Genes Analyzed for their Possible Association with Human Longevity
| Gene symbol | Name | Genomic location | Population | Study design | Conclusions | Reference | External links |
|---|---|---|---|---|---|---|---|
| ABCA1 | ATP-binding cassette, sub-family A (ABC1), member 1 | 9q31.1 | Japanese | The R219K SNP was examined in 256 centenarians and 190 healthy younger controls | The allelic frequencies were not different between the two groups | Arai et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | French | I/D polymorphism was examined in centenarians (n = 338) and in adults aged 20-70 years | A variant of ACE which predisposes to coronary heart disease was more frequent in centenarians with a significant increase of the homozygous genotype | Schachter et al., 1994 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | English, Cambridge | I/D polymorphism was examined in 182 women and 100 men aged >84 years and in 100 boys and 100 girls younger than 17 years | The I/I polymorphism was depleted in the elderly males but not in the elderly females. Furthermore, significant differences were observed between ACE genotypes in elderly men and elderly women. | Galinsky et al., 1997 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Copenhagen, Denmark | ACE (I/D) polymorphism was examined in 10,150 subjects from 20 to >80 years-old | The relative frequency of the D allele did not change as a function of age | Agerholm-Larsen et al., 1997 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | French | I/D polymorphism was examined in 394 French centenarians (13% men and 87% women) and controls (238) from 20 to 70 years of age (140 men and 98 women) | Both the ACE D allele and ACE D/D genotype were more frequent in centenarians in comparison with controls, without sex-related differences nor significant correlation with a cardiovascular pathology | Faure-Delanef., 1998 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Dutch, Leiden | I/D polymorphism was determined in 648 subjects >85 years-old | The ACE genotype distributions were similar in elderly and young subjects | Heijmans et al., 1999 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Danish | I/D polymorphism was examined in 187 centenarians and 201 controls (20-64 years) | No significant differences relative to longevity were found | Bladbjerg et al., 1999 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | American Caucasians, USA | I/D polymorphism was examined in 2689 healthy Caucasians: 17-39 years (n = 979; 505 males and 474 females), 40-59 years (n = 900; 526 males and 374 females), and 60-85 years (n = 810; 530 males and 280 females) | No statistically significant decrease in genotype or allele frequency was observed among carriers of ACE D | Hessner et al., 2001 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | French | I/D polymorphism was examined in 560 centenarians and 560 adult controls | No association was observed between ACE allele frequencies or genotype and longevity | Blanche et al., 2001 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Danish | The I/D polymorphisms were examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | No significant differences relative to longevity were found | Tan et al., 2001 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Polish | I/D polymorphism was examined in 101 long-life subjects and in a group of 494 younger persons | No connection was made between polymorphism and long-life | Grzeszczak et al., 2002 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Uighur, Kazakh and Han, Xin Jiang Uighur Autonomous region of China | I/D polymorphism was examined in 424 subjects comprising 227 Uighur individuals, 108 Kazakh individuals, and 89 Han individuals. All subjects in the latter two groups ranged in age from 65 to 70 years, whereas the Uighur subjects comprised two different age groups: those ranging in age from 59 to 70 years and those ranging in age from 90 to 113 years. | Within the Uighur group, frequency of the D allele was significantly higher in the group aged >90 than in the group aged <70. The overall distributions of alleles in the three groups did not differ significantly. | Rahmutula et al., 2002 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Brazilian population of European and Japanese origin | I/D polymorphism was examined in 834 persons aged 10-104 years | An association between the DD genotype and D allele and age was observed in the European group only. The ACE polymorphism-age association occurred at age >60 years in the European population with decreasing II frequency. | Da Cruz et al., 2003 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Danish | The cognitive skills of 684 twins aged 73+ years were examined in relation to a polymorphic 287 bp fragment in the ACE gene that can be present in the insertion (I) variant and absent in the deletion (D) variant | Neither physical nor cognitive performance was associated with the ACE genotype. Having the D allele, however, improved the chances of survival. | Fredericsen et al., 2003 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Korean | I/D polymorphism was examined in 103 centenarians (13 men and 90 women) and in 7232 apparently healthy adults (4100 men and 3132 women) | The frequencies of genotypes and alleles of the centenarians were not significantly different from those of the control groups. There was also a lack of association between the presence of the D allele and dementia status. | Choi et al., 2003 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Northern and Southern Europe | I/D polymorphism was examined in 82 centenarians and 252 middle-aged, unrelated subjects or volunteers | No statistically significant differences were found in ACE genotype or allele frequencies between centenarians and controls in Southern European population | Panza et al., 2003 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Russian, Novosibirsk | I/D polymorphism was examined in 97 elderly subjects and control group aged 25-64 | Frequency of D/D genotype among senile and long-living men was significantly lower than in men 55-64 years of age. A similar decrease of this gene frequency was also found in women of the same age. | Shabalin et al., 2003 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Xinjiang Uygur people, China | I/D polymorphisms of ACE gene were examined in 42 centenarians, 102 people aged 90-99, 70 people aged 65-70, and 53 cases of natural death aged 65-70 used as controls | The frequency rates of genotype D/D and D alleles were significantly higher in the centenarian group than in the controls | Wufuer et al., 2004 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Italian | The genotype and allele frequency distribution of I/D polymorphisms were analyzed in 235 Italian patients with sporadic Alzheimer disease, 153 with familial Alzheimer disease, 192 healthy controls and 111 centenarians | There were no significant differences in ACE genotypes or allele frequencies in all the studied groups. Centenarians show the highest allele D frequency, although the value is not significant. | Nacmias et al., 2006 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Columbian | Polymorphisms in the ACE gene were analyzed in a sample of 538 subjects (18-106 years) | A significant decrease in DD genotype (24 vs. 16%) was observed between young and old subject groups (mean age: 45 vs. 77 years). The ACE DD genotype and D allele decrease was significant only in women. | Forrero et al., 2006 | Entrez Gene Ensembl HapMap |
| ACE | Angiotensin I-Converting Enzyme | 17q23.3 | Southern Italian | The association of sex and age with the occurrence of ACE genotypes in healthy aging and longevity in 1344 healthy individuals and 64 centenarians was examined | A significant association of D allele and age was observed in centenarians | Seripa et al., 2006 | Entrez Gene Ensembl HapMap |
| AGT | Angiotensinogen (serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 8) | 1q42.2 | Danish | M/T235 SNP was examined in 187 centenarians and 201 controls (20-64 years) | No significant differences relative to longevity were found | Bladbjerg et al., 1999 | Entrez Gene UniGene Ensembl HapMap |
| AGT | Angiotensinogen (serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 8) | 1q42.2 | Danish | M/T235 SNP was examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | Significant influences on survival in males were observed, with reduced hazards of death for carriers of the M235 allele | Tan et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| APOA1 | Apolipoprotein A-I | 11q23.3 | Southern Italy | APOA1-MspI-RFLP (-75 nt from the transcription starting site) polymorphism was examined in a healthy population with 304 subjects aged 18-45 years, 267 subjects aged 46-80 years and 229 subjects aged 81-109 years (including 184 subjects, 43 males and 141 females, older than 100 years) | The APOA1 allele P, which increases serum LDL-C at middle-age and is over-represented in cardiovascular diseases, tends to increase its frequency in the centenarians males | Garasto et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| APOA4 | Apolipoprotein A-IV | 11q23.3 | Italian | Two restriction polymorphisms, HinfI347 (Thr347/Ser) and Fnu4HI360 (Gln360/His), and a VNTR (alleles 3, 4) at the 3 region of the APOA4 gene were examined in 71 centenarians (18 men and 53 women, 100-107 years of age, mean 102.3 years) and 100 unrelated adults (21 men and 79 women, 19-59 years of age, mean 35.7 years) | The Hinf347 genotype distribution was significantly different in centenarians | Pepe et al., 1998 | Entrez Gene UniGene Ensembl HapMap |
| APOA4 | Apolipoprotein A-IV | 11q23.3 | French | Glutamine (CAG) to histidine (CAT) substitution at codon 360 was examined in 120 Alzheimer patients (88 females, 32 males) and 119 presumed-healthy elderly subjects (62 females, 57 males) | The frequency of apoAIV alleles was not significantly different between Alzheimer patients and the elderly control group. However, in both groups, apoAIV (360:His) allele frequency was higher than in the general population. | Merched et al., 1998 | Entrez Gene UniGene Ensembl HapMap |
| APOA4 | Apolipoprotein A-IV | 11q23.3 | Southern Italy | APOA4-HincII-RFLP (Asp127/Ser127) polymorphism was examined in a healthy population with 304 subjects aged 18-45 years, 267 subjects aged 46-80 years and 229 subjects aged 81-109 years (including 184 subjects, 43 males and 141 females, older than 100 years) | No significant differences relative to longevity were found | Garasto et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| APOB | Apolipoprotein B (including Ag(x) antigen) | 2p24.1 | Finnish | The apolipoprotein B Xba I polymorphism was examined in 179 Finnish centenarians | The frequencies of the Xba I alleles among the centenarians and among the young Finns were not significantly different | Louhija et al., 1994 | Entrez Gene UniGene Ensembl HapMap |
| APOB | Apolipoprotein B (including Ag(x) antigen) | 2p24.1 | Finnish | The apolipoprotein B EcoRI and Xba I polymorphisms were examined in Finnish nonagenarians | The frequency of EcoRI allele R- was low in the nonagenarians, whereas the allele frequency for the Xba I polymorphism did not differ between the nonagenarians and the younger groups | Kervinen et al., 1994 | Entrez Gene UniGene Ensembl HapMap |
| APOB | Apolipoprotein B (including Ag(x) antigen) | 2p24.1 | Italian | A sample of 143 centenarians and a control sample of 158 individuals were examined for polymorphism in APOB restriction fragment length (RFLP) (XbaI2488 and EcoRI4154) and variable number of tandem repeat (VNTR) (3'APOB-VNTR) polymorphisms | Neither the XbaI-RFLP nor the EcoRI-RFLP was able to discriminate between centenarians and controls, while the 3'APOB-VNTR multiallelic system revealed significant differences between the samples: the frequency of alleles with fewer than 35 repeats was lower in centenarians than in controls | de Benedictis et al., 1997 | Entrez Gene UniGene Ensembl HapMap |
| APOC1 | Apolipoprotein C-I | 19q13.31 | English, Cambridge | Allele and genotype frequencies at Hpa1 RFLP were examined in 182 women and 100 men aged >84 years and in 100 boys and 100 girls younger than 17 years | Allele and genotype frequencies were significantly different in the elderly women compared to the younger sample. No difference was observed in the elderly men. | Galinsky et al., 1997 | Entrez Gene Ensembl HapMap |
| APOC3 | Apolipoprotein C-III | 11q23.3 | Finnish | The Sst I polymorphism was examined in 179 Finnish centenarians | The S2 allele (Sst I restriction site present) occurred more often in the centenarians (frequency, 12.9%) than in the youngest reference population (frequency, 8.8%) | Louhija et al., 1994 | Entrez Gene UniGene Ensembl HapMap |
| APOC3 | Apolipoprotein C-III | 11q23.3 | Russian | 5'-untranslated region (T-455C) SNP was examined in a group of 137 elderly individuals (70-106 years old) | A greater frequency of the -455C allele was demonstrated with aging | Anisimov et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| APOC3 | Apolipoprotein C-III | 11q23.3 | Southern Italian | APOC3-SstI-RFLP polymorphism was examined in a healthy population of 304 subjects aged 18-45 years, 267 subjects aged 46-80 years and 229 subjects aged 81-109 years (including 184 subjects, 43 males and 141 females, older than 100 years) | No significant differences relative to longevity were found | Garasto et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| APOC3 | Apolipoprotein C-III | 11q23.3 | Ashkenazi Jews | A group of centenarians (213), their offspring (216), and an age-matched control group (258) were genotyped for 66 polymorphisms in 36 candidate genes related to cardiovascular disease | The prevalence of homozygosity for the 641C allele in the APOC3 promoter (rs2542052) was higher in centenarians (25%) and their offspring (20%) than in controls (10%). This genotype was associated with significantly lower serum levels of APOC3, a favorable pattern of lipoprotein levels and sizes. A lower prevalence of hypertension and greater insulin sensitivity in the 641C homozygotes was also found. | Atzmon et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Swedish | Isoforms were examined in 407 healthy Swedish individuals, 244 men and 163 women, ages 17 to 86 years | The E4 frequency decreased with increasing age and was significantly lower in individuals > 60 years of age | Eggertsen et al., 1993 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | French | Common polymorphism was examined in centenarians (n = 338) and in adults aged 20-70 years | E4 allele was significantly less frequent in centenarians than in controls, while the frequency of the E2 allele was significantly increased | Schachter et al., 1994 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Finnish | The common polymorphism of apolipoprotein E (E2, E3, and E4) was examined in 179 Finnish centenarians | The frequency of the E2 allele was higher and that of the E4 allele lower in the centenarians | Louhija et al., 1994 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Finnish | The common polymorphism of apolipoprotein E (E2, E3, and E4) was examined in Finnish nonagenarians | The frequency of the E4 allele was lower in the nonagenarians than in the middle-aged and young adults | Kervinen et al., 1994 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Italian | Polymorphism (E2, E3, and E4) was examined in a sample of 228 healthy Italian subjects (124 men and 104 women) aged 18-93 | The frequency of E4 decreased with age and was not found in subjects aged 75 and older | Ruiu et al., 1995 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | English, Cambridge | Common polymorphism was examined in 182 women and 100 men aged > 84 years and in 100 boys and 100 girls younger than 17 years | Difference between genotypes in the elderly women and the young sample was observed. However, this did not retain significance when the genotype frequencies of the young sample were adjusted to values expected from the allele frequencies on the basis of Hardy-Weinberg equilibrium and compared to observed genotypes in elderly men and women. | Galinsky et al., 1997 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | French | Polymorphism (E2, E3, and E4) was examined in 560 centenarians and 560 adult controls | Significant differences were observed between centenarians and controls for allelic and genotypic frequencies. The E4E4 genotype was under-represented in centenarians compared to controls. Centenarians carrying at least one E2 allele or homozygous for E3 were more frequent than controls. | Blanche et al., 2001 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Uygur nationality in Xinjiang China | Polymorphism (E2, E3, and E4) was studied in 164 subjects including 35 persons aged 90 years or older, 71 men aged 20-35 and 54 men with myocardial infarction | There was statistically significant difference in the E4 allele frequencies among the three groups with the older group showing a lower E4 allele frequency | Wang et al., 2001 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Finnish | Common polymorphism was examined in 179 persons (28 men and 151 women) aged 100 years and older | The percentages of E2-allele carriers increased with age, particularly in women. The percentage of carriers of the E4 allele was lower than expected. | Frisoni et al., 2001 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Brazilian | Common polymorphism was examined in 70 elderly patients aged 80 years or more | No association was observed between the genotypes and longevity, though individuals with the E3E4 genotype had a mean age greater than those with the E3E3 genotype. | Schwanke et al., 2002 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Russian, Novosibirsk | Common polymorphism was examined in 97 elderly subjects and control group aged 25-64 | In men aged 83 years and older the frequency of the E3/E4 genotype was lower and that of the E2/E3 genotype was higher. In subjects of senile age and long-livers of both sexes genotype E4/E4 was not found. | Shabalin et al., 2003 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Korean | Common polymorphism was examined in 103 centenarians (13 men and 90 women, mean age 102.4 +/- 2.6 years) and in 6435 adults (5008 men and 1427 women) of mean age 50.7 +/- 7.9 years | The frequencies of genotypes and alleles of the centenarians were not significantly different from those of the control groups. The frequency of the E4 allele was significantly higher in centenarians with dementia than in centenarians without definitive dementia. | Choi et al., 2003 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Ashkenazi Jews, Jerusalem | Common polymorphism was examined in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and a group of 441 younger subjects (22 years) | Ashkenazi older subjects were characterized by an increased percentage of the E2 allele and a decreased percentage of the E4 allele | Stessman et al., 2005 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Uygur nationality in Xinjiang China | Common polymorphism was examined in centenarians (n=42), 90-year-old people (n=102), 65-70-year-old people (n=70) and controls(n=53). | The frequencies of genotype E3/4 and E4, E3 alleles in the centenarian group were significantly lower than those in controls, whereas the frequencies of genotype E2/3 and E2 allele in the centenarian group were significantly higher than those in controls. | Mayila et al., 2005 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Columbian | Polymorphisms were studied in a sample of 538 Colombian subjects (aged 18-106 years) | There were no differences between young and old subjects | Forrero et al., 2006 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Southern Italian | The association of sex and age with the occurrence of APOE genotypes in healthy aging and longevity in 1344 healthy individuals and 64 centenarians was examined | A higher E2 frequency was observed in men aged 60-90 years and in centenarians | Seripa et al., 2006 | Entrez Gene Ensembl HapMap |
| APOE | Apolipoprotein E | 19q13.31 | Greek | The prevalence of genotypes in 80 healthy aged individuals (>80 years) and 391 adults (median age 43 years) was examined | Genotypes were comparable in both groups with the exception of E3/3 and E3/4, which were significantly higher and lower, respectively, in aged individuals. The epsilon2 and epsilon3 allele frequencies were not different between the groups. The epsilon4 allele was significantly less frequent in aged individuals compared to controls. | Stakias et al., 2007 | Entrez Gene Ensembl HapMap |
| AKAP10 | A kinase (PRKA) anchor protein 10 | 17p11.2 | European-American | Male (n= 4766) and female (n = 6202) divided into young (18-39 years) and old (60 years) groups were examined for polymorphisms | A polymorphism that results in an amino acid change from Ile to Val showed the strongest correlation with age. The Val variant was associated with a statistically significant decrease in the length of the electrocardiogram PR interval. An A to G polymorphism in the 3'UTR of D-AKAP2 showed a significant decrease of the G allele in the older sample of both genders. Additionally, the I646V polymorphism was found to be significantly different between young and old in both males and females. | Kammerer et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| BF | B-factor, properdin | Italian | Alleles were examined in healthy aged people (77 centenarians and 89 elderly subjects) | The frequencies of the alleles were similar in the studied cohorts | Bellavia et al., 1999 | Ensembl HapMap |
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| BRCA1 | Breast cancer 1, early onset | 17q21.31 | New England Caucasians and Italian | Polymorphisms were examined in 102 centenarians from the New England area and 84 centenarians from Italy. The control population consisted of 97 individuals from Italy. | The genotype "a+a" was more frequent in both centenarian groups compared to the control group whereas the genotype "a+b" was less frequent. The results, however, were not statistically significant. | Vijg et al., 2000 | Entrez Gene UniGene Ensembl HapMap |
| C3 | Complement component 3 | 19p13.3 | Italian | C3 alleles were examined in healthy aged people (77 centenarians and 89 elderly subjects) | The frequencies of C3 alleles were similar in the studied cohorts | Bellavia et al., 1999 | Entrez Gene UniGene Ensembl HapMap |
| C4 | Complement component 4 | Italian | C4 alleles were examined in healthy aged people (77 centenarians and 89 elderly subjects) | The frequencies of C4A alleles were similar in the studied cohorts. For C4B null allele (C4BQ0) a trend toward an increase in the older cohort was observed, although the differences were not significant after statistical correction. | Bellavia et al., 1999 | Ensembl HapMap |
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| CAT | Catalase | 11p13 | Danish | The -262C/T polymorphism was examined in 2223 Danish individuals aged 45-93 years | The -262C/T polymorphism was not associated with survival | Christiansen et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| CPB2 | Carboxypeptidase B2 (plasma, carboxypeptidase U) | 13q14.13 | American Caucasian | Genotypes were studied in 2224 men and women aged 65 or older at baseline | During 10 years of follow-up, men with the -438 A/A genotype had decreased mortality due to all causes, and lived, on average, longer than men with the -438 G allele. The effects of -438 G/A in women were smaller and not statistically significant. | Reiner et al., 2005 | Entrez Gene Ensembl HapMap |
| CETP | Cholesteryl ester transfer protein | 16q13 | Ashkenazi Jews | The I405V polymorphism distribution was examined in 213 Ashkenazi Jews with exceptional longevity (mean [SD] age, 98.2 [5.3] years), their offspring (n = 216; mean [SD] age, 68.3 [6.7] years) and in an age-matched control group of Ashkenazi Jews (n = 258) + participants from the Framingham Offspring Study (n = 589) | Probands with exceptional longevity showed an increased frequency of homozygosity for the 405 valine allele of (VV genotype) compared with controls | Barzilai et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| CETP | Cholesteryl ester transfer protein | 16q13 | Japanese | Polymorphisms (mutations in intron 14 and exon 15, and Taq1B) were examined in 256 centenarians and 190 healthy younger controls (22-65 years old) | The allelic frequencies did not differ between the two groups | Arai et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| CETP | Cholesteryl ester transfer protein | 16q13 | Italian | The I405V polymorphism was examined in 175 Italian centenarians and, as a control group, 189 sex-matched healthy individuals | No association with longevity was found | Cellini et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| CNDP1 | Carnosine dipeptidase 1 (metallopeptidase M20 family) | 18q22.3 | German | The frequency of CNDP1 alleles in German centenarians (n=330), patients with premature coronary heart disease, and matched controls was examined. A total of 1382 individuals were examined. | There was no difference in allele or genotype frequency between centenarians and their control group, or between cardiovascular patients and their control group | Zschocke et al., 2006 | Entrez Gene Ensembl HapMap |
| CYP1A1 | Cytochrome P450, family 1, subfamily A, polypeptide 1 | 15q24.1 | Northern Italian | SNP was examined in 94 nonagenarians and centenarians and 418 control subjects of younger age | No association with longevity was found | Taioli et al., 2001 | Entrez Gene Ensembl HapMap |
| CYP1A1 | Cytochrome P450, family 1, subfamily A, polypeptide 1 | 15q24.1 | German, Bonn | T461N and 3801 T/ C SNPs were examined in 205 octogenarians and a reference group of 294 persons aged less than 80 years | No association with longevity was found | Pesch et al., 2004 | Entrez Gene Ensembl HapMap |
| CYP1B1 | Cytochrome P450, family 1, subfamily B, polypeptide 1 | 2p22.2 | German, Bonn | V432L SNP was examined in 205 octogenarians and a reference group of 294 persons aged less than 80 years | In octogenarians, the 432L allele was less prevalent than in the reference group | Pesch et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| CYP2E1 | Cytochrome P450, family 2, subfamily E, polypeptide 1 | 10q26.3 | Spanish | The enzymatic polymorphism was examined in 41 nonagenarians (10 males, mean age 92.2 years, range 90-98) free of known malignancies or neurodegenerative diseases and in control groups comprised of 137 (116 males, mean age 32 years) | No association with longevity was found | Agundez et al., 1997 | Entrez Gene UniGene Ensembl HapMap |
| CYP2D6 | Cytochrome P450, family 2, subfamily D, polypeptide 6 | Spanish | The enzymatic polymorphism was examined in 41 nonagenarians (10 males, mean age 92.2 years, range 90-98) free of known malignancies or neurodegenerative diseases and in control groups comprised of 217 healthy volunteers (128 males, mean age 36.3 years) | No association with longevity was found | Agundez et al., 1997 | Ensembl HapMap |
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| CYP2D6 | Cytochrome P450, family 2, subfamily D, polypeptide 6 | French | CYP2D63 (A2637 deletion) and CYP2D64 (G1934A transition) alleles were examined in 552 centenarians and 243 controls aged 20-70 years | No significant difference was found between centenarian and control subjects | Muiras et al., 1998 | Ensembl HapMap |
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| F2 | Coagulation factor II (thrombin) | 11p11.2 | Danish | F2 20210 G/A SNP was examined in 187 centenarians and 201 controls (20-64 years) | No association with longevity was found | Bladbjerg et al., 1999 | Entrez Gene Ensembl HapMap |
| F2 | Coagulation factor II (thrombin) | 11p11.2 | Danish | F2 20210 G/A SNP was examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | No association with longevity was found | Tan et al., 2001 | Entrez Gene Ensembl HapMap |
| F2 | Coagulation factor II (thrombin) | 11p11.2 | American Caucasians | F2 20210 G/A SNP was examined in 2689 healthy Caucasians aged 17-39 years (n = 979; 505 males and 474 females), 40-59 years (n = 900; 526 males and 374 females), and 60-85 years (n = 810; 530 males and 280 females) | No statistically significant decrease in genotype or allele frequency was observed among carriers of F2 | Hessner et al., 2001 | Entrez Gene Ensembl HapMap |
| F5 | Coagulation factor V (proaccelerin, labile factor) | 1q24.2 | American Caucasian | G1691A SNP was examined in 2689 healthy Caucasians aged 17-39 years (n = 979; 505 males and 474 females), 40-59 years (n = 900; 526 males and 374 females), and 60-85 years (n = 810; 530 males and 280 females) | No statistically significant decrease in genotype or allele frequency was observed among carriers of F5 | Hessner et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| F7 | Coagulation factor VII (serum prothrombin conversion accelerator) | 13q34 | Italian | The R353Q substitution polymorphism in exon 8 was examined in 124 healthy individuals over 100 years of age and 130 young, healthy individuals | No significant differences relative to longevity were found | Mannucci et al., 1997 | Entrez Gene UniGene Ensembl HapMap |
| F7 | Coagulation factor VII (serum prothrombin conversion accelerator) | 13q34 | Danish | The R353Q substitution, intron 7 (37bp)n, and -323ins10 polymorphisms were examined in 187 centenarians and 201 healthy controls, aged 20-64 years (mean age 42 years). | The genotype frequencies in the centenarians and in the controls were similar | Bladbjerg et al., 1999 | Entrez Gene UniGene Ensembl HapMap |
| F7 | Coagulation factor VII (serum prothrombin conversion accelerator) | 13q34 | Danish | Blood coagulation factor VII (FVII) R/Q353 and FVII-323ins10 SNPs were examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | R/Q353 and FVII-323ins10 manifest significant influences on survival in males, with reduced hazards of death for carriers of the Q353 allele and the FVII-323P10 allele | Tan et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| F7 | Coagulation factor VII (serum prothrombin conversion accelerator) | 13q34 | Danish | Polymorphisms were examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | No association with longevity was found | Tan et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| F7 | Coagulation factor VII (serum prothrombin conversion accelerator) | 13q34 | Ashkenazi Jews, Jerusalem | Arg/Gln R353Q SNP was examined in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and a group of 441 younger subjects (22 years) | There was a decrease in the percentage of the A allele in older Ashkenazi male subjects and a corresponding marked decrease (9.7-2.1%) in the percentage of AA homozygotes | Stessman et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| FAS | Fas (TNF receptor superfamily, member 6) | 10q23.31 | Northern Italian | The -670 and -1377 position SNPs were examined in 50 centenarians and 86 young controls | Genotype and allele distribution for both polymorphisms were similar in controls and centenarians | Pinti et al., 2002 | Entrez Gene UniGene Ensembl HapMap |
| FASLG | Fas ligand (TNF superfamily, member 6) | 1q25.1 | Northern Italian | The -124 and 169 position SNPs were examined in 50 centenarians and 86 young controls | Genotype and allele distribution for both polymorphisms were similar in controls and centenarians | Pinti et al., 2002 | Entrez Gene UniGene Ensembl HapMap |
| FCGR2A | Fc fragment of IgG, low affinity IIa, receptor (CD32) | 1q23.3 | German | The FCGR2A-His131Arg polymorphism was analyzed in a group of 408 German centenarians and two samples of younger Germans aged 60-75 and 18-49 years | No statistically significant differences were observed between the three age groups | Flesch et al., 2006 | Entrez Gene Ensembl HapMap |
| FGB | Fibrinogen beta chain | Italian | The G/A-455 SNP was examined in 124 healthy individuals over 100 years old and 130 young, healthy individuals | Alleles and genotypes were found with similar frequencies in centenarians and in the control group | Mannucci et al., 1997 | Ensembl HapMap |
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| FGB | Fibrinogen beta chain | Danish | The -455G/A SNP was examined in 187 centenarians and 201 healthy controls aged 20-64 years (mean age 42 years) | The genotype frequencies in the centenarians and the controls were similar | Bladbjerg et al., 1999 | Ensembl HapMap |
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| FGB | Fibrinogen beta chain | Danish | The G/A-455 SNP was examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | No association with longevity was found | Tan et al., 2001 | Ensembl HapMap |
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| FGB | Fibrinogen beta chain | American Caucasian | Genotypes for -455 G/A were studied in 2224 men and women aged 65 years and older at baseline | During 10 years of follow-up, no association with survival was found | Reiner et al., 2005 | Ensembl HapMap |
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| FOXO1A | Forkhead box O1A (rhabdomyosarcoma) | 13q14.11 | Italian | The (T/C, 97347 bp) polymorphism was examined in healthy people 17-85 yr of age (n= 278; mean age, 54.8; 76 males and 202 females) and in healthy people 86-109 yr of age (n= 218; mean age, 98.0; 56 males and 162 females | No significant differences relative to longevity were found | Bonafe et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| FOXO1A | Forkhead box O1A (rhabdomyosarcoma) | 13q14.11 | Japanese | 3 intronic polymorphisms were examined in 122 Japanese semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33) | No significant differences relative to longevity were found | Kojima et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| GH1 | Growth hormone 1 | 17q23.3 | Dutch, Leiden | Intron 4 A/T SNP was examined in 1576 individuals aged 85 and older | Female carriers of the A allele had reduced height and mortality | Heemst et al., 2005 | Entrez Gene Ensembl HapMap |
| GHRHR | Growth hormone releasing hormone receptor | 7p14.3 | Dutch, Leiden | Codon 57 A/G SNP was examined in 1576 individuals aged 85 and older | No association with longevity was found | Heemst et al., 2005 | Entrez Gene Ensembl HapMap |
| GP1BA | Glycoprotein Ib (platelet), alpha polypeptide | 17p13.2 | Danish | The L/P codon 33 SNP was examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | No association with longevity was found | Pesch et al., 2004 | Entrez Gene Ensembl HapMap |
| GSTM1 | Glutathione S-transferase M1 | 1p13.3 | French | The GSTM1 deletion was examined in 552 centenarians and 243 controls aged 20-70 years | No significant difference was found between centenarian and control subjects | Muiras et al., 1998 | Entrez Gene UniGene Ensembl HapMap |
| GSTM1 | Glutathione S-transferase M1 | 1p13.3 | Northern Italian | GSTM1 deletion was examined in 94 nonagenarians and centenarians and 418 control subjects of younger age | No association with longevity was found | Taioli et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| GSTM1 | Glutathione S-transferase M1 | 1p13.3 | German, Bonn | GSTM1 deletion was examined in 205 octogenarians and a reference group of 294 persons aged less than 80 years | Octogenarians turned out to have a marginally significant more GSTM1 negatives | Pesch et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| GSTM1 | Glutathione S-transferase M1 | 1p13.3 | Danish | The GSTM1 deletion polymorphism was examined in a longitudinal study of 681 elderly Danish twins (234 men and 447 women) | A non-significant trend for carriage of two copies of the GSTM1 functional gene was found | Christiansen et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
| GSTP1 | Gutathione S-transferase pi | 11q13.2 | German, Bonn | I105V SNP was examined in 205 octogenarians and a reference group of 294 persons aged less than 80 years | There were fewer observed heterozygous 105IV genotypes and more homozygous 105VV genotypes than expected among octogenarians | Pesch et al., 2004 | Entrez Gene Ensembl HapMap |
| GSTT1 | Glutathione S-transferase theta 1 | 22q11.23 | Northern Italian | Deletion was examined in 94 nonagenarians and centenarians and 418 control subjects of younger age | A significant difference in the proportion of nonagenarians and centenarians homozygotes for the deletion was observed in comparison to control subjects | Taioli et al., 2001 | Entrez Gene Ensembl HapMap |
| GSTT1 | Glutathione S-transferase theta 1 | 22q11.23 | German, Bonn | Deletion was examined in 205 octogenarians and a reference group of 294 persons aged less than 80 years | Octogenarians had less GSTT1 deficient genotypes | Pesch et al., 2004 | Entrez Gene Ensembl HapMap |
| GSTT1 | Glutathione S-transferase theta 1 | 22q11.23 | Danish | Deletion polymorphism was examined in a longitudinal study of 681 elderly Danish twins (234 men and 447 women) | Both heterozygosity and homozygosity for the GSTT1 functional gene was associated with a moderate but significant increased mortality in women | Christiansen et al., 2006 | Entrez Gene Ensembl HapMap |
| HFE | Hemochromatosis | 6p22.2 | Sicilian | C282Y, H63D and S65C polymorphisms were studied in 106 young controls (age range from 22 to 55 years; 40 men and 66 women) and 35 elderly subjects (age range from 91 to 105 years; seven men and 28 women) | A significant difference was observed only in women in frequencies of C282Y alleles between the young and the elderly subjects. Concerning H63D polymorphisms, no significant differences were observed, between old and young people. | Lio et al., 2002 | Entrez Gene UniGene Ensembl HapMap |
| HFE | Hemochromatosis | 6p22.2 | Sardinian | The C282Y, H63D and S65C SNPs were examined in 61 controls and 57 centenarians | Although there was a trend for an increased frequency of the H63D allele in centenarian women, no significant differences were observed in frequencies of the different alleles between young and centenarians | Carru et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| HLA-A1 | Major histocompatibility complex, class I, A1 | Irish, Belfast | 100 control samples (59% female, 41% male with an age-range of 19-45 years old) and 93 aged samples (70% female, 30% male with an age-range of 80-97 years old) were examined | No age-related allele or genotype frequencies were observed | Ross et al., 2003 | Ensembl HapMap |
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| HLA-A1 | Major histocompatibility complex, class I, A1 | Bulgarian | 12 alleles were examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | The most frequent HLA alleles in elderly Bulgarians were A01 and A02. A number of haplotypes were also found to be more frequent in elderly Bulgarians compared to the controls. | Naumova et al., 2004 | Ensembl HapMap |
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| HLA-DRB1 | Major histocompatibility complex, class II, DR beta 1 | Japanese, Okinawa | Polymorphisms in Okinawan centenarians were analyzed | DRB1*1401 allele was significantly increased in the centenarians while DRB1*0101 and DRB1*1201 alleles were slightly decreased | Akisaka et al., 1997 | Ensembl HapMap |
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| HLA-DRB1 | Major histocompatibility complex, class II, DR beta 1 | French | The longevous groups included two independent cohorts totalling 533 centenarians and 163 nonagenarian siblings. Control group included 2950 subjects. | DR7 frequency was elevated in longevous men and DR13 frequency was increased in centenarians. DR11's influence on longevity displayed a significant interaction with sex, with an increase in women from longevous sibships. HLA-DR homozygotes were more frequent in centenarians than in controls. | Ivanova et al., 1998 | Ensembl HapMap |
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| HLA-DRB1 | Major histocompatibility complex, class II, DR beta 1 | Bulgarian | 10 alleles were examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | The most frequent HLADRB1 alleles in elderly Bulgarians were DRB111 and DRB113. The most frequent haplotypes in elderly Bulgarians compared to the controls were DRB111-DQB103 and DRB113-DQB106. | Naumova et al., 2004 | Ensembl HapMap |
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| HLA-DRB1 | Major histocompatibility complex, class II, DR beta 1 | Mexican | A total of 71 healthy elders were studied, age ranged from 80 to 96 years (mean 86.2 years). The control samples were obtained from 99 young (from 21 - 54 years; mean 35.2 years) healthy individuals unrelated to elders. | A significant increased frequency of HLA-DRB1*11 was found in elderly women whereas this allele was not present in elderly males | Soto-Vega et al., 2005 | Ensembl HapMap |
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| HLA-DRB3 | Major histocompatibility complex, class II, DR beta 3 | Irish, Belfast | 100 control samples (59% female, 41% male with an age-range of 19-45 years old) and 93 aged samples (70% female, 30% male with an age-range of 80-97 years old) were examined | No age-related allele or genotype frequencies were observed | Ross et al., 2003 | Ensembl HapMap |
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| HLA-DRB5 | Major histocompatibility complex, class II, DR beta 5 | Dutch, Leiden | 964 inhabitants aged 85 years and over and 2444 young controls, aged 20-35 years, with an identical ethnic and demographic background were examined | HLA-DR5 was higher in the group of 85 years and over, as compared to the control group | Lagaay et al., 1991 | Ensembl HapMap |
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| HLA-DQA1 | Major histocompatibility complex, class II, DQ alpha 1 | Japanese, Okinawa | Polymorphisms in HLA class II alleles of Okinawan centenarians were analyzed | DQA10101=0104 and DQA105 alleles were significantly increased in the centenarians | Akisaka et al., 1997 | Ensembl HapMap |
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| HLA-DQA1 | Major histocompatibility complex, class II, DQ alpha 1 | Mexican | A total of 71 healthy elders were studied, age ranged from 80 to 96 years (mean 86.2 years). The control samples were obtained from 99 young (from 21 - 54 years; mean 35.2 years) healthy individuals unrelated to elders. | The frequencies of the alleles tested were not statistically different among groups | Soto-Vega et al., 2005 | Ensembl HapMap |
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| HLA-DQA1 | Major histocompatibility complex, class II, DQ alpha 1 | Sardinian | 129 centenarians and 154 sexagenarians randomly selected from the inhabitants of the same province were examined. In addition, 24 85-year-old sibs of centenarians were enrolled. | Sib pair analysis showed nonsignificant differences between the observed and expected percentage of DQA* allele sharing | Scola et al., 2006 | Ensembl HapMap |
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| HLA-DQB1 | Major histocompatibility complex, class II, DQ beta 1 | Japanese, Okinawa | Polymorphisms in HLA class II alleles of Okinawan centenarians were analyzed | DQB105 and DQB103 alleles were significantly increased in the centenarians | Akisaka et al., 1997 | Ensembl HapMap |
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| HLA-DQB1 | Major histocompatibility complex, class II, DQ beta 1 | Bulgarian | 5 alleles were examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | The most frequent DQB1 alleles in elderly Bulgarians were DQB103 and DQB105 | Naumova et al., 2004 | Ensembl HapMap |
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| HLA-DQB1 | Major histocompatibility complex, class II, DQ beta 1 | Sardinian | 129 centenarians and 154 sexagenarians randomly selected from the inhabitants of the same province were examined. In addition, 24 85-year-old sibs of centenarians were enrolled. | Sib pair analysis showed nonsignificant differences between the observed and expected percentage of DQB1* allele sharing. | Scola et al., 2006 | Ensembl HapMap |
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| HLA-B | Major histocompatibility complex, class I, B | Dutch, Leiden | 964 inhabitants aged 85 years and over and 2444 young controls, aged 20-35 years, with an identical ethnic and demographic background were examined | HLA-B40 was lower in the group of 85 years and over, as compared to the control group | Lagaay et al., 1991 | Ensembl HapMap |
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| HLA-B | Major histocompatibility complex, class I, B | 6p21.33 | Irish, Belfast | 100 control samples (59% female, 41% male with an age-range of 19-45 years old) and 93 aged samples (70% female, 30% male with an age-range of 80-97 years old) were examined | No age-related allele or genotype frequencies were observed | Ross et al., 2003 | Entrez Gene Ensembl HapMap |
| HLA-B | Major histocompatibility complex, class I, B | 6p21.33 | Bulgarian | 14 alleles were examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | The most frequent HLB alleles in elderly Bulgarians were B18 and B*51 | Naumova et al., 2004 | Entrez Gene Ensembl HapMap |
| HLA-B | Major histocompatibility complex, class I, B | 6p21.33 | Mexican | 71 healthy elders were studied, age ranged from 80 to 96 years (mean 86.2 years). The control samples were obtained from 99 young (from 21 - 54 years; mean 35.2 years) healthy individuals unrelated to elders. | The frequencies of the alleles tested were not statistically different among groups | Soto-Vega et al., 2005 | Entrez Gene Ensembl HapMap |
| HLA-C | Major histocompatibility complex, class I, C | 6p21.33 | Bulgarian | 10 alleles were examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | The most frequent HLC alleles in elderly Bulgarians were C*07 and C*04 | Naumova et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| HMOX1 | Heme oxygenase (decycling) 1 | 22q12.3 | Japanese | A (GT)n repeat polymorphism in the promoter region of the human HO-1 gene was examined in younger (60 years, 59 male and 45 female) and older (60-75 years, 95 male and 106 female) subjects | The proportion of allelic frequencies in class L with a large size of (GT)n repeat, as well as the genotypic frequencies in group I with class L alleles, was significantly lower in the oldest male subjects than in the younger males. In contrast, in the oldest female subjects this was not observed. | Yamaya et al., 2003 | Entrez Gene Ensembl HapMap |
| HSPA1A | Heat shock 70kDa protein 1A | Southern Italian | (A/C)-110 polymorphism was examined in 591 subjects (263 males and 328 females; age range 18-109 years; 36 male and 84 female centenarians) | A significant age-related decrease of the frequency of allele (A)-110 was observed in females, while no difference was observed in the males | Altomare et al., 2003 | Ensembl HapMap |
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| HSPA1A | Heat shock 70kDa protein 1A | Danish | The -110A/C polymorphism was examined in a cohort of aged Danish twins (individuals aged between 70 and 91 years, categorized according to the presence or absence of various diseases) | An association was found between low self-rated health and heterozygosity (AC genotype) | Singh et al., 2004 | Ensembl HapMap |
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| HSPA1A | Heat shock 70kDa protein 1A | Ashkenazi Jews | rs1043618 polymorphism was examined in 347 centenarians, 260 centenarian offspring, and 238 controls | No genetic associations were found with two SNPs within two hsp70 genes | Terry et al., 2006 | Ensembl HapMap |
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| HSPA1A | Heat shock 70kDa protein 1A | Danish | The A/C -110 polymorphism was examined in 426 participants of various ages | Female carriers of CC genotype survive better than the noncarriers (AA and AC) | Singh et al., 2006 | Ensembl HapMap |
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| HSPA1B | Heat shock 70kDa protein 1B | Danish | The A/G (1267 coding) polymorphism was examined in 426 participants of various ages | Female carriers of GG genotype survive better than noncarriers | Singh et al., 2006 | Ensembl HapMap |
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| HSPA1B | Heat shock 70kDa protein 1B | Ashkenazi Jews | rs6457452 polymorphism was examined in 347 centenarians, 260 centenarian offspring, and 238 controls | No genetic associations were found | Terry et al., 2006 | Ensembl HapMap |
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| HSPA1L | Heat shock 70kDa protein 1-like | Irish | The frequency of the T2437C transversion (Met to Thr) polymorphism was investigated in a healthy aged population of 100 control samples (59% female, 41% male with an age-range of 19-45 years) and 129 aged consecutive samples (70% female, 30% male with an age range of 80-97 years) | The 2437T polymorphic nucleotide was observed to increase in the elderly, although not attaining statistical significance. The TT genotype was observed to be significantly increased within the aged population, while conversely the TC genotype was significantly decreased in the aged subjects. | Ross et al., 2003 | Ensembl HapMap |
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| HSPA1L | Heat shock 70kDa protein 1-like | Danish | The T/C (2437 coding) polymorphism was examined in a cohort of aged Danish twins (individuals aged between 70 and 91 years, categorized according to the presence or absence of various diseases) | No association with longevity was found | Singh et al., 2004 | Ensembl HapMap |
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| IFNG | Interferon gamma | 12q15 | Italian | The distribution of 874T/A polymorphism was examined in 174 Italian centenarians (>99 years old, 142 women and 32 men) and 248 <60-year-old control subjects (90 women and 158 men) | The +874T allele, known to be associated with low IFN-gamma production, was found less frequently in centenarian women than in centenarian men or in control women whereas no significant differences were observed in the distribution of the two alleles between male or female controls. Allele frequencies in centenarian men were not found significantly different from male controls. | Lio et al., 2002 | Entrez Gene UniGene Ensembl HapMap |
| IFNG | Interferon gamma | 12q15 | Sardinian | 112 (36 male, 76 female) centenarians, as well as 137 sixty-year-old controls, were analyzed for 874T/A SNP | No significant differences were observed in centenarians and controls | Pes et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| IFNG | Interferon gamma | 12q15 | Irish | 100 control samples (59% female and 41% male) and 93 aged consecutive samples (70% female, 30% male with an age range of 80-97 years) were analyzed for Intron I microsatellite repeats | No significant differences were observed in centenarians and controls | Ross et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IFNG | Interferon gamma | 12q15 | Bulgarian | 874T/A SNP was examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | No significant association with longevity was found | Naumova et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| IGF1 | Insulin-like growth factor 1 (somatomedin C) | Dutch, Leiden | CA repeat (promoter) and CT repeat (intron 2) were examined in 1576 individuals aged >85 | CA repeats (191 bp minor allele) seem to contribute most to female longevity | Van Heemst et al., 2005 | Ensembl HapMap |
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| IGF2 | Insulin-like growth factor 2 (somatomedin A) | 11p15.5 | Italian | exon 9 AvaII RFLP polymorphism was examined in 219 centenarians (72 males and 147 females) and 256 (controls 20-70 years, 119 males and 137 females) | No significant difference between centenarians and controls was observed | De Luca et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| IGF2 | Insulin-like growth factor 2 (somatomedin A) | 11p15.5 | Ashkenazi Jews, Jerusalem | A/G ApaI site SNP was examined in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and a group of 441 younger subjects (22 years) | An increase in the A allele was observed in older Ashkenazi females and a highly significant increase was observed in the AA genotype in these subjects | Stessman et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| IGF1R | Insulin-like growth factor 1 receptor | 15q26.3 | Italian | The G/A, codon 1013 polymorphism was examined in healthy people 17-85 yr of age (n= 278; mean age, 54.8; 76 males and 202 females) and in healthy people 86-109 yr of age (n= 218; mean age, 98.0; 56 males and 162 females | The analysis revealed lower free IGF-I plasma levels in IGF1R A subjects (AG and AA genotypes) than in A- (GG genotype) subjects. A subjects were more represented among long-lived people than in young people. | Bonafe et al., 2003 | Ensembl HapMap |
| IL1A | Interleukin 1, alpha | 2q13 | Finnish | 250 (52 males and 198 females) nonagenarians and 400 healthy control group (18-60 years old) were examined for 889 SNP | No significant differences relative to longevity were found | Wang et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| IL1A | Interleukin 1, alpha | 2q13 | Nothern and Central Italian | The -889 C/T SNP was examined in 1131 unrelated individuals aged 20-102 years (453 females and 678 males, including 94 female and 40 male centenarians) | No significant differences in the genotype and allele frequency distributions were observed between young, elderly and centenarian subjects | Cavallone et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IL1B | Interleukin 1, beta | 2q13 | Finnish | 250 (52 males and 198 females) nonagenarians and 400 healthy control group blood donors (18-60 years old) were examined for +3953 and -511 SNPs | No significant differences relative to longevity were found | Wang et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| IL1B | Interleukin 1, beta | 2q13 | Norhern and Central Italian | -511 C/T SNP was examined in 1131 unrelated individuals aged 20-102 years (453 females and 678 males, including 94 female and 40 male centenarians) | No significant differences in the genotype and allele frequency distributions were observed between young, elderly and centenarian subjects | Cavallone et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IL1B | Interleukin 1, beta | 2q13 | Japanese | -511 C/T SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) | No association with longevity was found | Okayama et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| IL1RN | Interleukin 1 receptor antagonist | 2q13 | Finnish | 250 (52 males and 198 females) nonagenarians and 400 healthy control (18-60 years old) were examined for VNTR polymorphism in intron 2 (an 86 bp repeat sequence) | No significant differences relative to longevity were found | Wang et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| IL1RN | Interleukin 1 receptor antagonist | 2q13 | Northern and Central Italian | The 86-bp repeated sequence in intron 2 was examined in 1131 unrelated individuals aged 20-102 years (453 females and 678 males, including 94 female and 40 male centenarians) | No significant differences in the genotype and allele frequency distributions were observed between young, elderly and centenarian subjects | Cavallone et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IL2 | Interleukin 2 | 4q27 | Irish | 100 control samples (59% female and 41% male) and 93 aged consecutive samples (70% female, 30% male with an age range of 80-97 years) were analyzed for -330 T/G SNP | No significant difference between centenarians and controls was observed | Ross et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IL2 | Interleukin 2 | 4q27 | Central and Southern Italian | 330T/G SNP was examined in 168 centenarians and 214 control subjects matched for age and ancestry | No significant difference between centenarians and controls was observed | Scolla et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Italian | 700 individuals (482 women and 218 men), ranging from 60 to 110 years of age including 323 centenarians were subdivided into three age-groups (60-80, 81-99 and over 99 years of age), and were assessed for -174 C/G locus variability | The proportion of homozygotes for the G allele decreases in centenarian males, but not in centenarian females. Among males, homozygotes for the G allele have higher IL-6 serum levels in comparison with carriers of the C allele. | Bonafe et al., 2001 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Finnish | 250 (52 males and 198 females) nonagenarians and 400 healthy control group (18-60 years old) were examined for -174, +3953 and -511 SNPs | No significant differences relative to longevity were found | Wang et al., 2001 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Northern Irish | 100 and 93 octogenarian and nonagenarian subjects + 182 control subjects (41% male, 59% female) were examined for -174 polymorphism | The frequency of GG homozygotes decreases with age by about 10% compared with young controls. CC homozygotes have higher serum levels of IL-6 levels compared with GG. | Rea et al., 2003 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Irish | 100 control samples (59% female and 41% male) and 93 aged consecutive samples (70% female, 30% male with an age range of 80-97 years) were analyzed for -174G/C SNP | No significant difference between centenarians and controls was observed | Ross et al., 2003 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Sardinian | 112 (36 male, 76 female) centenarians from the island of Sardinia, as well as 137 sixty-year-old controls were analyzed for -174G/C SNP. | No significant difference between centenarians and controls was observed | Pes et al., 2004 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | South Italian | 2174 G/C promoter polymorphism was examined in a population of 81 centenarians compared with a control group of 122 middle-aged healthy subjects | No differences were found in allele and genotype frequencies between centenarians and controls | Capurso et al., 2004 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Danish | Three SNPs (-597G/A, -572G/C and -174G/C) and the AT-stretch polymorphism (-373(A)n(T)m) were examined in 1710 Danish subjects ranging in age from 47 to 100 years | A modest, but significant, increase in the frequency of -174GG homozygotes with age was observed. However, this increase is mainly followed by a concomitant decrease in GC heterozygotes rather than in CC homozygotes, as may be expected if the C allele is associated with decreased survival chance. | Christiansen et al., 2004 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Bulgarian | -174G/C SNP was examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | GC genotype was higher in elders while GG genotype was lower in elders | Naumova et al., 2004 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Japanese | -634 C/G SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) | No association with longevity was found | Okayama et al., 2005 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | American Caucasian | Genotypes for -174 G/C were studied in 2224 men and women aged 65 years and older at baseline | During 10 years of follow-up, a possible interaction between anti-inflammatory drugs, -174 C/C genotype, and longevity was found | Reiner et al., 2005 | Entrez Gene Ensembl HapMap |
| IL6 | Interleukin 6 | 7p15.3 | Finnish | The promoter (-174G/C) SNP was examined in 285 nonagenarians (representing mortality between 90 and 95 years of age) | The frequency of allele G was higher in the survivors (n = 114) than in the non-survivors (n = 171) | Hurme et al., 2005 | Entrez Gene Ensembl HapMap |
| IL10 | Interleukin 10 | 1q32.2 | Finnish | 250 (52 males and 198 females) nonagenarians and 400 healthy control group (18-60 years old) were examined for 1082 SNP | No significant differences relative to longevity were found | Wang et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| IL10 | Interleukin 10 | 1q32.2 | Italian | The -1082G/A, -819C/T and -592C/A proximal promoter SNPs were examined in 190 centenarians (>99 years old, 159 women and 31 men) and in 260 control subjects (99 women and 161 men less than 60 years old) | The -1082G homozygous genotype, associated with high IL-10 production, was increased in centenarian men but not in centenarian women. No difference was found between centenarians and control subjects regarding the other two SNPs. | Lio et al., 2002 | Entrez Gene UniGene Ensembl HapMap |
| IL10 | Interleukin 10 | 1q32.2 | Irish | 100 control samples (59% female and 41% male) and 93 aged consecutive samples (70% female, 30% male with an age range of 80-97 years) were analyzed for -1082G/A SNP | No significant differences were observed in centenarians and controls | Ross et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IL8 | Interleukin 8 | 4q13.3 | Irish | 100 control samples (59% female and 41% male) and 93 aged consecutive samples (70% female, 30% male with an age range of 80-97 years) were analyzed for Intron 1 A/T SNP | No significant differences were observed in centenarians and controls | Ross et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IL10 | Interleukin 10 | 1q32.2 | Italian | -1082 G/A SNP was examined in 72 centenarian men, 102 centenarian women and healthy unrelated controls (115 men and 112 women, aged 22-60 years) | The number of male centenarians homozygous for the -1082G genotype, suggested to be associated with high IL-10 production, was significantly increased in comparison with younger control subjects. No significant differences were observed between women and controls. | Lio et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IL10 | Interleukin 10 | 1q32.2 | Sardinian | 112 (36 male, 76 female) centenarians, as well as 137 sixty-year-old controls, were analyzed for -1082G/A SNP | No significant differences were observed in centenarians and controls | Pes et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| IL10 | Interleukin 10 | 1q32.2 | Bulgarian | -1082G/A, -819 C/T and -592 C/A SNPs were examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | Genotype -1082G/A, -819 C/C, -592 C/C was positively associated, while genotype -1082A/A, -819 C/T, -592 C/A, was negatively associated with longevity in Bulgarians. The results, however, were not statistically significant. | Naumova et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| IL10 | Interleukin 10 | 1q32.2 | Japanese | -819 T/C SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) | There was a significant association of -819 T/C with age | Okayama et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| IL12 | Interleukin 12 | Irish | 100 control samples (59% female and 41% male) and 93 aged consecutive samples (70% female, 30% male with an age range of 80-97 years) were analyzed for Exon 8 A/T SNP | No significant differences were observed in centenarians and controls | Ross et al., 2003 | Ensembl HapMap |
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| IL18 | Interleukin 18 | 11q23.1 | Japanese | -607 A/C SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) | -607 A/C polymorphism is gender age associated but not in a significant manner | Okayama et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| IL18 | Interleukin 18 | 11q23.1 | American | Three polymorphisms were tested in 1671 participants aged 65-80 years | IL-18 concentrations were found to be associated with physical function and the C allele of the rs5744256 polymorphism was associated with reduced serum concentrations and with shorter walk times | Frayling et al., 2007 | Entrez Gene UniGene Ensembl HapMap |
| INS | Insulin | 11p15.5 | Italian | FokI RFLP polymorphism was examined in 219 centenarians (72 males and 147 females) and 256 (controls 20-70 years, 119 males and 137 females). | No significant difference between centenarians and controls was observed | De Luca et al., 2001 | Entrez Gene Ensembl HapMap |
| INS | Insulin | 11p15.5 | Dutch, Leiden | VNTR repeat (promoter) was examined in 1576 individuals aged >85 | No significant association with longevity was found | Heemst et al., 2005 | Entrez Gene Ensembl HapMap |
| INSR | Insulin receptor | 19p13.2 | Japanese | 5 intronic and 1 exonic polymorphisms were examined in 122 semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33) | One haplotype, which was comprised of 2 intronic SNPs in linkage disequilibrium, was more frequent in semisupercentenarians than in younger controls | Kojima et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| IRS1 | Insulin receptor substrate 1 | 2q36.3 | Italian | G/A, codon 972 polymorphism was examined in healthy people 17-85 yr of age (n= 278; mean age, 54.8; 76 males and 202 females) and in healthy people 86-109 yr of age (n= 218; mean age, 98.0; 56 males and 162 females | No significant differences relative to longevity were found. | Bonafe et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| IRS1 | Insulin receptor substrate 1 | 2q36.3 | Japanese | 2 exonic polymorphisms were examined in 122 Japanese semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33) | No significant differences relative to longevity were found | Kojima et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| IRS1 | Insulin receptor substrate 1 | 2q36.3 | Dutch, Leiden | Codon 972 A/G SNP was examined in 1576 individuals aged >85 | Arg allele seems to contribute to longevity in females | Heemst et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| ITGA2 | Integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) | 5q11.2 | American Caucasian | GPIa C807T SNP was examined in 2689 healthy Caucasians aged 17-39 years (n = 979; 505 males and 474 females), 40-59 years (n = 900; 526 males and 374 females), and 60-85 years (n = 810; 530 males and 280 females) | No statistically significant decrease in genotype or allele frequency was observed | Hessner et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| ITGB3 | Integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) | 17q21.32 | Danish | L/P33 SNP was examined in 187 Danish centenarians and 201 healthy controls aged 20-64 years (mean age 42 years) | No significant association with longevity was found | Bladbjerg et al., 1999 | Entrez Gene UniGene Ensembl HapMap |
| ITGB3 | Integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) | 17q21.32 | American Caucasian | T1565C SNP was examined in 2689 healthy Caucasians aged 17-39 years (n = 979; 505 males and 474 females), 40-59 years (n = 900; 526 males and 374 females), and 60-85 years (n = 810; 530 males and 280 females) | The Pl(A2) allele frequency significantly decreased with age | Hessner et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| KIR | Killer cell immunoglobulin-like receptors | Irish | 24 genotypes were examined in 93 aged individuals (80-97 years) and 100 controls (19-45 years) | A comparison of the frequency of individual KIR gene repertoires within the aged subset and control group failed to reveal a statistically significant level of genotypic variation | Maxwell et al., 2004 | Ensembl HapMap |
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| KIR | Killer cell immunoglobulin-like receptors | Irish | A 22 bp deletion was examined in 180 aged individuals (90-97 years) and 180 controls (19-45 years) | There was no observed association between this common polymorphic variation and the aged Irish population | Ross et al., 2004 | Ensembl HapMap |
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| KL | Klotho | 13q13.1 | Bohemian Czechs, Baltimore Caucasians, and Baltimore African-Americans | Amino acid substitutions F352V and C370S SNPs were examined in 435 elderly individuals (>75 years) and 611 contemporary newborns (Bohemian Czech), 965 elderly individuals (>65 years) and 646 control infants (Baltimore Caucasians and Baltimore African-Americans) | Homozygous elderly individuals were underrepresented in all populations | Arking et al., 2002 | Entrez Gene UniGene Ensembl HapMap |
| LIPC | Lipase, hepatic | 15q21.3 | Japanese | C-514T SNP was examined in 256 centenarians and 190 healthy younger controls | The allelic frequencies were not different between the two groups | Arai et al., 2003 | Entrez Gene Ensembl HapMap |
| LPL | Lipoprotein lipase | 8p21.3 | Japanese | PvuII and HindIII polymorphisms were examined in 256 centenarians and 190 healthy younger controls | The allelic frequencies were not different between the two groups | Arai et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| LTA | Lymphotoxin alpha (TNF superfamily, member 1) | 6p21.33 | Irish, Belfast | 100 control samples (59% female, 41% male with an age-range of 19-45 years old) and 93 aged samples (70% female, 30% male with an age-range of 80-97 years old) were examined for 252A/G SNP | No age-related allele or genotype frequencies were observed | Ross et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| MEFV | Mediterranean fever | Sicilian | 3 MEFV associated mutations- M694V (A2080G), M694I (G2082A), and V726A (T2177C) were examined in 121 patients affected by acute myocardial infarction (AMI), 68 centenarians, and 196 age-matched controls from Sicily. | The proinflammatory M694V (A2080G) mutation was over-represented significantly in CHD patients and under-represented in oldest old, and intermediate values were in healthy, young controls | Grimaldi et al., 2006 | Ensembl HapMap |
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| MLH1 | mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) | 3p22.3 | Korean | 3 SNPs in the coding region were analyzed in 85 Korean centenarians and in 106 Korean controls | The CAT haplotype (C670, A676 and T1172) frequency was significantly higher in the centenarians than in the controls | Kim et al., 2006 | Entrez Gene Ensembl HapMap |
| MMP1 | Matrix metallopeptidase 1 (stromelysin 1, progelatinase) | 11q22.2 | Japanese | -1607 1G/2G SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) | -1607 1G/2G was not found to be longevity associated | Okayama et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| MMP3 | Matrix metallopeptidase 3 (stromelysin 1, progelatinase) | 11q22.2 | Japanese | -1171 5A/6A SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) | -1171 5A/6A polymorphism is gender age associated but not in a significant manner | Okayama et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| MT1A | Metallothionein 1A (functional) | Italian | Polymorphisms A/C (Asp/Thr) transition at 647 nt position and A/G (Lys/Arg) transition at 1,245 nt position were examined | For the +647 polymorphism, old and very old female with Asp/Asp genotype display reduced IL-6 plasma concentrations and the allele Asp is more involved in longevity | Cipriano et al., 2006 | Ensembl HapMap |
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| MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | 1p36.22 | English, Cambridge | The 677C/T SNP was examined in 182 women and 100 men aged > 84 years and in 100 boys and 100 girls younger than 17 years | MTHFR allele and genotype frequencies were similar in the elderly and young populations | Galinsky et al., 1997 | Entrez Gene UniGene Ensembl HapMap |
| MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | 1p36.22 | Swiss | C677T SNP was examined in healthy subjects (n=118; age<65), older healthy subjects (n=106; age>65), patients with coronary artery disease (n=75), and patients with peripheral arterial occlusive disease (n=63) | No difference in either genotype distribution or allele frequencies between patients and controls was found | Todesco et al., 1999 | Entrez Gene UniGene Ensembl HapMap |
| MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | 1p36.22 | Danish | A/V114 SNP was examined in 187 unselected centenarians, and 201 healthy controls aged 20-64 years (mean age 42 years) | No significant association with longevity was found | Bladbjerg et al., 1999 | Entrez Gene UniGene Ensembl HapMap |
| MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | 1p36.22 | American Caucasian | C677T SNP was examined in 2689 healthy Caucasians aged 17-39 years (n = 979; 505 males and 474 females), 40-59 years (n = 900; 526 males and 374 females), and 60-85 years (n = 810; 530 males and 280 females) | No statistically significant decrease in genotype or allele frequency was observed among carriers of 677T | Hessner et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | 1p36.22 | Danish | A/V codon 114 SNP was examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | No significant association with longevity was found | Pesch et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | 1p36.22 | Ashkenazi Jews, Jerusalem | C677T SNP was examined in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and a group of 441 younger subjects (22 years) | There is an increase in C allele frequency (67.4% versus 55.3%) in the older Ashkenazi females and an increase in the percentage of CC homozygotes | Stessman et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| MTTP | Microsomal triglyceride transfer protein (large polypeptide, 88kDa) | 4q23 | Danish | 1651 participants in the Danish 1905 cohort study (aged 92-93 years) were genotyped for two SNPs (rs2866164 and Q95H). Furthermore, a group of 575 middle-aged Danish twins (mean age 53.7 years) were tested as a younger control group. | The risk haplotype had no significant survival disadvantage after 6.5 years of follow-up. The distributions of the suggested risk alleles and the resulting haplotypes were not statistically different between the two age cohorts. | Bathum et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| MTTP | Microsomal triglyceride transfer protein (large polypeptide, 88kDa) | 4q23 | German | rs1800591, rs2866164, and Q/H 95 SNPs were examined in 1,039 unrelated individuals between 95 and 109 years of age (mean age, 98.2 years); 373 (36%) of the long-lived participants were centenarians or supercentenarians (mean age, 101.4 years). The sex ratio in the entire sample was 74% females vs. 26% males. A total of 540 control individuals aged between 60 and 75 years (mean age, 67.2 years) were used. | No evidence for association was detected between any of the tested SNPs at the allele or at the genotype level | Nebel et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| MTTP | Microsomal triglyceride transfer protein (large polypeptide, 88kDa) | 4q23 | Dutch, Leiden | -493G/T and Q95H allele and haplotype frequencies were examined in 379 nonagenarians, 525 of their offspring, and 251 partners of their offspring and in 655 octogenarians and 244 young controls | No association with longevity was found | Beekman et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
| MTR | 5-methyltetrahydrofolate-homocysteine methyltransferase | 1q43 | German | 329 healthy individuals were examined for 2576A-->G (D919G) polymorphism | Prevalence of the G-allele was significantly higher in the older than in the younger individuals. Separate analysis of female and male subjects revealed that the influence of the MTR genotype on male subjects became relevant at a younger age as opposed to female subjects suggesting a gender-dependent effect. | Linnebank et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| NAT2 | N-acetyltransferase 2 (arylamine N-acetyltransferase) | 8p22 | Spanish | The enzymatic polymorphism was examined in 41 nonagenarians (10 males, mean age 92.2 years, range 90-98) free of known malignancies or neurodegenerative diseases and in control groups comprised of 217 healthy volunteers (128 males, mean age 36.3 years) | No association with longevity was found | Agundez et al., 1997 | Entrez Gene UniGene Ensembl HapMap |
| NAT2 | N-acetyltransferase 2 (arylamine N-acetyltransferase) | 8p22 | French | NAT25A (C481T), NAT26A (G590A), NAT27A (G857A), and NAT214A (G191A) SNPs were examined in 552 centenarians and 243 controls aged 20-70 years | No significant difference was found between centenarian and control subjects with respect to allelic variant frequencies, genotype distributions or predicted phenotypes deduced from genotype combinations | Muiras et al., 1998 | Entrez Gene UniGene Ensembl HapMap |
| NR3C1 | Nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) | 5q31.3 | Dutch | The ER22/23EK polymorphism was studied in 402 men with a mean age of 77.8 years | After a follow-up of 4 years, 73 (19%) of 381 noncarriers died, while none of the 21 ER22/23EK carriers had died. Carriers may have lower C-reactive protein levels. | van Rossum et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| NR3C1 | Nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) | 5q31.3 | Dutch, Leiden | 552 participants were genotyped for the ER22/23EK, N363S and BclI polymorphisms | No associations with cardiovascular pathologies, all cause and cardiovascular mortality were observed for any of the polymorphisms. | Kuningas et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
| PARP1 | Poly (ADP-ribose) polymerase family, member 1 | 1q42.12 | Italian | Polymorphic repeats in exon 1 were examined in 196 centenarians (143 females and 53 males) and 358 controls (196 females and 162 male; 10-85 years old) | No significant difference in genotypic frequencies was found between centenarians and controls | de Benedictis et al., 1998 | Entrez Gene UniGene Ensembl HapMap |
| PARP1 | Poly (ADP-ribose) polymerase family, member 1 | 1q42.12 | French | 324 centenarians and 324 controls were examined for C402T (exon 2), T1011C(exon7), G1215A (exon 8) and T2444C (exon 17) SNPs | No association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity was observed | Cottet et al., 2000 | Entrez Gene UniGene Ensembl HapMap |
| PIK3CB | Phosphoinositide-3-kinase, catalytic, beta polypeptide | 3q22.3 | Italian | T/C, 359 bp and A/G, 303 bp polymorphisms were examined in healthy people 17-85 yr of age (n= 278; mean age, 54.8; 76 males and 202 females) and in healthy people 86-109 yr of age (n= 218; mean age, 98.0; 56 males and 162 females | No significant differences relative to longevity were found, though some differences in genotype combinations with IGF1R were observed | Bonafe et al., 2003 | Entrez Gene Ensembl HapMap |
| PIK3CB | Phosphoinositide-3-kinase, catalytic, beta polypeptide | 3q22.3 | Japanese | 2 promoter and 1 intron polymorphisms were examined in 122 semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33) | No significant differences relative to longevity were found | Kojima et al., 2004 | Entrez Gene Ensembl HapMap |
| PIK3CG | Phosphoinositide-3-kinase, catalytic, gamma polypeptide | Japanese | 1 intronic polymorphism was examined in 122 semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33) | No significant differences relative to longevity were found | Kojima et al., 2004 | Ensembl HapMap |
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| PLAT | Plasminogen activator, tissue | 8p11.21 | Danish | Intron 8 insertion 311 polymorphism was examined in 187 Danish centenarians, and 201 healthy Danish blood donors, aged 20-64 years (mean age 42 years) | No significant differences relative to longevity were found | Bladbjerg et al., 1999 | Entrez Gene Ensembl HapMap |
| PLAT | Plasminogen activator, tissue | 8p11.21 | Danish | Intron 8 insertion 311 polymorphism was examined in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | No significant differences relative to longevity were found | Pesch et al., 2004 | Entrez Gene Ensembl HapMap |
| PON1 | Paraoxonase 1 | 7q21.3 | Italian | A Leucine (L allele) to Methionine (M allele) substitution at codon 55, and a Glutamine (A allele) to Arginine (B allele) substitution at codon 192 were examined in 579 people aged 20 to 65 years old, and 308 centenarians | The percentage of carriers of the B allele at codon 192 is higher in centenarians than in controls (0.539 vs 0.447), though this was due to an increase of people carrying M alleles at codon 55 | Bonafe et al., 2002 | Ensembl HapMap |
| PON1 | Paraoxonase 1 | 7q21.3 | French | Polymorphism at codon 192 (Gln/Arg) was examined in 256 healthy Caucasian men (69.8 +/- 4.0 years) | Gln homozygotes are more frequent in aging than Arg allele carriers | Xia et al., 2003 | Ensembl HapMap |
| PON1 | Paraoxonase 1 | 7q21.3 | Sicilian | The promoter T(-107)C and coding region Gln192Arg (Q192R) and Leu55Met (L55M) polymorphisms were examined in 100 healthy octogenarians and 200 adults | Octagenerians displayed significant higher levels of PON1 activity and had an higher percentage of (-107)CC compared with controls. No difference in the L55M and Q192R genotypes distribution was found in both groups. | Campo et al., 2004 | Ensembl HapMap |
| PON1 | Paraoxonase 1 | 7q21.3 | Italian and N. Irish | PON1 55 (L/M) and 192 (Q/R) polymorphisms were studied in 308 Italian centenarians and 579 adult controls and 296 Irish octo/nonagenarians and 296 young controls | There was a significant difference in 192 genotypes in Italian centenarians compared to younger controls and a similar but non-significant trend between octo/nonagenarian and young subjects in Ireland. Distribution of the 55 (L/M) polymorphism frequencies were similar in both groups. | Rea et al., 2004 | Ensembl HapMap |
| PON1 | Paraoxonase 1 | 7q21.3 | Danish | Two coding polymorphisms, 55M/L and 192Q/R, and a promoter variant, -107C/T, were studied in 1932 Danish individuals aged 47-93 years | A cross-sectional study comparing the genotype distribution of the three polymorphisms as well as the haplotype distribution in different age groups did not reveal any difference. However, a longitudinal follow-up study on survival in the same sample indicated that 192RR homozygotes have a poorer survival of coronary heart disease compared to QQ homozygotes. | Christiansen et al., 2004 | Ensembl HapMap |
| PPARG | Peroxisome proliferative activated receptor, gamma | 3p25.2 | Italian | The Pro/Ala polyporphism at codon 12 was studied in 222 long-lived subjects and 250 aged subjects | A different genotype frequency was observed between long-lived and aged men; no differences were observed in the two age groups of women. | Barbieri et al., 2004 | Entrez Gene Ensembl HapMap |
| PPARGC1A | Peroxisome proliferative activated receptor, gamma, coactivator 1, alpha | 4p15.2 | Japanese | 2 exonic polymorphisms were examined in 122 semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33) | No significant differences relative to longevity were found | Kojima et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| REN | Renin | 1q32.1 | Italian | Polymorphic repeats in intron 7 (Short and Long alleles) were examined in 196 centenarians (143 females and 53 males) and 358 controls (196 females and 162 male; 10-85 years old) | No significant difference in genotypic frequencies was found between centenarians and controls | de Benedictis et al., 1998 | Entrez Gene UniGene Ensembl HapMap |
| SERPINE1 | Serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 7q22.1 | Italian | The 1-bp guanine deletion/insertion (4G/5G) polymorphism in the promoter region was examined in 124 healthy individuals >100 years old and 130 young, healthy individuals | In centenarians there was a significantly higher frequency of the 4G allele and of the homozygous 4G4G genotype associated with high PAI-1 (SERPINE1) levels | Mannucci et al., 1997 | Entrez Gene Ensembl HapMap |
| SERPINE1 | Serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 7q22.1 | Dutch, Leiden | The 1-bp guanine deletion/insertion (4G/5G) polymorphism in the promoter region was examined in 648 subjects >85 years old | In the cross-sectional analysis, the genotype distributions were similar in elderly and young subjects | Heijmans et al., 1999 | Entrez Gene Ensembl HapMap |
| SERPINE1 | Serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 7q22.1 | Danish | The 1-bp guanine deletion/insertion (4G/5G) polymorphism was examined in 187 centenarians and 201 healthy controls aged 20-64 years (mean age 42 years) | No significant differences relative to longevity were found | Bladbjerg et al., 1999 | Entrez Gene Ensembl HapMap |
| SERPINE1 | Serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 7q22.1 | German, Bonn | 205 donors (147 women, 58 men; aged 80-98 years, mean 86.1) were examined for the 1-bp guanine deletion/insertion (4G/5G) polymorphism in the promoter region | The 4G/5G polymorphism was not found to be associated with longevity | Lottermoser et al., 2001 | Entrez Gene Ensembl HapMap |
| SERPINE1 | Serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 7q22.1 | Danish | The 1-bp guanine deletion/insertion (4G/5G) polymorphism was examined in the promoter region in 187 centenarians (47 males and 140 females) and 201 controls (20-64 years) | No significant differences relative to longevity were found | Pesch et al., 2004 | Entrez Gene Ensembl HapMap |
| SERPINE1 | Serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 7q22.1 | American Caucasian | Genotypes for -675 4G/5G were studied in 2224 men and women aged 65 years and older at baseline | 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women | Reiner et al., 2005 | Entrez Gene Ensembl HapMap |
| SERPINE1 | Serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 7q22.1 | Sicilian, Italian | The distribution of AAT allele variants was examined in 127 young patients affected by acute myocardial infarction (AMI), 255 young controls and 143 centenarians | The Z allele frequency was most frequent in centenarians, intermediate in healthy young controls and less frequent in AMI patients. The heterozygous MZ genotype was significantly over-represented in centenarians and under represented in AMI patients with intermediate values in young controls (16/255). | Listi et al., 2006 | Entrez Gene Ensembl HapMap |
| SIRT1 | sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) | 10q21.3 | German | Five SNPs, distributed across the entire gene, including the promoter region, were genotyped in 1573 long-lived individuals (centenarians and nonagenarians) and matched younger controls | No evidence for an association was detected between any of the tested SNPs and the longevity phenotype at the allele, genotype or haplotype levels | Flachsbart et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| SIRT3 | Sirtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) | 11p15.5 | Southern Italian | G477T exon 3 SNP was examined in 801 unrelated subjects: 331 males and 470 females (120 centenarians: 36 males and 84 females) and controls 18-60 years old | In males the TT genotype increases, while the GT genotype decreases survival in the elderly | Rose et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| SIRT3 | Sirtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) | 11p15.5 | Southern Italian | A VNTR polymorphism (72-bp repeat core) in intron 5 was analyzed in 945 subjects (312 males and 391 females of 20- to 80-year-old and 242 subjects 90- to 106-year-old, median age 102 years) | The VNTR region has an allele specific enhancer activity. The allele completely lacking enhancer activity (allele 2) is virtually absent in males older than 90 years. | Bellizi et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | 1q22 | Japanese | 12 SNPs within a 10-kb region encompassing the entire SHC1 gene were examined in 230 Japanese centenarians and 180 healthy younger controls | The SNPs were not associated with longevity | Kamei et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| SHC1 | SHC (Src homology 2 domain containing) transforming protein 1 | 1q22 | Dutch, Leiden | Two independent cohorts of respectively 730 and 563 subjects aged 85 and over were tested for the association of Met(410)Val SNP with longevity using a prospective follow-up design | In the first cohort, increasing Val allele frequency was found with increasing age at death. Compared to Met/Met carriers, mortality rate was reduced in Met/Val carriers in the combined cohorts. | Mooijiaart et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| SOD2 | Superoxide dismutase 2, mitochondrial | 6q25.3 | Italian | 401C/T SNP was examined in 196 centenarians (143 females and 53 males) and 358 controls (196 females and 162 male; 10-85 years old) | No significant difference in genotypic frequencies was found between centenarians and controls | de Benedictis et al., 1998 | Entrez Gene Ensembl HapMap |
| SOD2 | Superoxide dismutase 2, mitochondrial | 6q25.3 | Ashkenazi Jews, Jerusalem | C9T; Ala (GCT) to Val (GTT) SNP was examined in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and a group of 441 younger subjects (22 years) | There was an increase in the percentage of T allele (51% versus 33.3%) in older Ashkenazi male subjects and a corresponding increase in the percentage (45.5% versus 25%) of TT homozygotes | Stessman et al., 2005 | Entrez Gene Ensembl HapMap |
| SOD2 | Superoxide dismutase 2, mitochondrial | 6q25.3 | Dutch, Leiden | Exon 16 C/T SNP was examined in 1576 individuals aged >85 | No association with reduced mortality risk was found | Heemst et al., 2005 | Entrez Gene Ensembl HapMap |
| SLC13A2 | Solute carrier family 13 (sodium-dependent dicarboxylate transporter), member 2 | American | The gene was sequenced in 13 subjects of age 90-99, 12 subjects between age 38-49 and 18 subjects age <23. The I550V polymorphism was genotyped in 2366 subjects and examined for its association with age. | An examination of 1338 female and 684 male white subjects demonstrated that the 1648 A/G (I550V) mutation was not associated with an increase in lifespan | Lee et al., 2003 | Ensembl HapMap |
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| SLC6A4 | Solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 | 17q11.2 | Japanese | Two alleles, 44-bp insertion (l allele) or deletion (s allele) in the promoter region, were examined in 265 Japanese centenarians and control subjects | The frequency of the l/l genotype and the l allele was significantly greater in centenarians than in younger control subjects, particularly women | Gondo et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| SULT1A1 | Sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1 | 16p11.2 | English, Nigerian | 638G/A (Arg 213 to His) SNP was examined in Caucasian (n=293; 12-99 years old) and African (Nigerian, n=52) populations | A significant age-related difference in genotype was observed within Caucasian population, with increasing incidence of SULT1A11 homozygosity and decreasing incidence of SULT1A12 homozygosity with increasing age | Coughtrie et al., 1999 | Entrez Gene Ensembl HapMap |
| TGFB1 | Transforming growth factor, beta 1 (Camurati-Engelmann disease) | 19q13.2 | Italian | 4 SNPs (-800 G/A, -509 C/T, +869 T/C and +915 G/C) were analysed in 419 subjects from Northern and Central Italy, including 172 centenarians and 247 younger controls | Significant differences were found at the +915 site as far as the C allele and GC genotype were concerned, both of them being lower in centenarians than in young controls, but none of the other tested genetic variants was significantly different between centenarians and controls. Moreover, a particular haplotype combination (G -800/C -509/C 869/C 915) was notably lower in centenarians than in younger individuals. | Carrieri et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| TGFB1 | Transforming growth factor, beta 1 (Camurati-Engelmann disease) | 19q13.2 | Bulgarian | Codons 10 (T/C) and 25 (G/C) SNPs were examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | No significant differences relative to longevity were found | Naumova et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| TGFB1 | Transforming growth factor, beta 1 (Camurati-Engelmann disease) | 19q13.2 | Japanese | +869 C/T SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) | The +869 C/T polymorphism was not found to be associated with longevity | Okayama et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| TGFB2 | transforming growth factor, beta 2 | 1q41 | Sicilian | The 1249-1250InsACAA/Non-Ins polymorphism distribution was examined in 88 celiac disease patients, 99 age- and sex-matched controls, and 28 95-year-old healthy subjects | No significant differences relative to longevity were found | Nuzzo et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
| TH | Tyrosine hydroxylase | 11p15.5 | Italian | Polymorphyc repeats in intron 1 (Short and Long alleles) were examined in 196 centenarians (143 females and 53 males) and 358 controls (196 females and 162 male; 10-85 years old) | A significant loss of LL homozygous genotypes was found at the THO locus in male but not in female centenarians with respect to matched controls | de Benedictis et al., 1998 | Entrez Gene UniGene Ensembl HapMap |
| TH | Tyrosine hydroxylase | 11p15.5 | Italian | An STR marker (HUMTHO1.STR) lies inside TH intron 1 a region involved in RNA alternative splicing of the TH primary transcript for generating four tissue specific types of mRNA. Association between HUMTHO1 variability (alleles 6, 7, 8, 9,10*, 10 as defined according to the number of repeats) and longevity was examined in the 210 centenarians (68 males and 142 females) and 755 controls (from 13 to 99 years). | Among all the alleles examined allele 10* (10 imperfect repeats) shows a remarkable dominant and beneficial effect in both heterozygous and homozygous genotypes that reduces the log hazard of death in an additive manner | Tan et al., 2002 | Entrez Gene UniGene Ensembl HapMap |
| TLR4 | toll-like receptor 4 | 9q33.1 | Italian | ASP299GLY polymorphism was examined | ASP299GLY polymorphism shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians show a higher frequency | Candore et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
| TNF | Tumor necrosis factor (TNF superfamily, member 2) | 6p21.33 | Finnish | 250 (52 males and 198 females) nonagenarians and 400 healthy control group (18-60 years old) were examined for -308 SNP | No significant differences relative to longevity were found | Wang et al., 2001 | Entrez Gene UniGene Ensembl HapMap |
| TNF | Tumor necrosis factor (TNF superfamily, member 2) | 6p21.33 | Italian | 308 G/A promoter SNP was examined in 72 centenarian men, 102 centenarian women and healthy unrelated controls (115 men and 112 women, aged 22-60 years) | The genotypic frequencies 308G and 308A, suggested to be associated with low and high TNF alpha production respectively, were not significantly different between centenarians and controls | Lio et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| TNF | Tumor necrosis factor (TNF superfamily, member 2) | 6p21.33 | Irish, Belfast | 100 control samples (59% female, 41% male with an age-range of 19-45 years old) and 93 aged samples (70% female, 30% male with an age-range of 80-97 years old) were examined for the -308A/G SNP | No age-related allele or genotype frequencies were observed | Ross et al., 2003 | Entrez Gene UniGene Ensembl HapMap |
| TNF | Tumor necrosis factor (TNF superfamily, member 2) | 6p21.33 | Danish | The -308 G/A SNP was examined in 122 centenarians, 174 octogenarians and 47 healthy volunteers aged 18 to 30 | The distribution of TNF-308 genotypes was not different across the three different age groups, but the GA genotype was associated with decreased prevalence of dementia in centenarians. The few centenarians with AA carrier status had higher mortality risk and tended to show higher plasma levels of TNF-alpha. | Bruunsgaard et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| TNF | Tumor necrosis factor (TNF superfamily, member 2) | 6p21.33 | Bulgarian | -308 (G/A) SNP was examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female) | No significant differences relative to longevity were found | Naumova et al., 2004 | Entrez Gene UniGene Ensembl HapMap |
| TNF | Tumor necrosis factor (TNF superfamily, member 2) | 6p21.33 | Japanese | -1031 T/C SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) | Though not statisticaly significant, the -1031 T/C polymorphism may be associated with age | Okayama et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| TNF | Tumor necrosis factor (TNF superfamily, member 2) | 6p21.33 | Mexican | The frequency of the -308 polymorphism was analyzed in 71 healthy elders, aged 80 to 96 years (mean 86.2 years). The control samples were obtained from 99 young (from 21 - 54 years; mean 35.2 years) healthy individuals unrelated to elders were studied, age ranged from 80 to 96 years (mean 86.2 years). | The TNF2 allele was increased in the elder group when compared to young controls | Soto-Vega et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| TP53 | Tumor protein p53 (Li-Fraumeni syndrome) | 17p13.1 | Northern Italian | GSTT1 (Glutathione S-transferase theta 1) deletion and the simultaneous presence of the three p53 polymorphisms were examined in 66 nonagenarians and centenarians in good health and in a sample of 150 young healthy volunteers of the same ethnic group | The absence of any p53 polymorphisms and of GSTT1 deletion, and the simultaneous presence of the three p53 polymorphisms and of GSTT1 deletion, were much more frequent in young subjects than in centenarians (41.5% versus 26.9% and 8.8% versus 3.8%, respectively). | Caspari et al., 2003 | Entrez Gene Ensembl HapMap |
| UCP2 | Uncoupling protein 2 (mitochondrial, proton carrier) | 11q13.4 | Dutch, Leiden | Promoter C/T SNP and 45 bp insertion/deletion (3'UTR) were examined in 1576 individuals aged >85 | No association with reduced mortality risk was found | Heemst et al., 2005 | Entrez Gene UniGene Ensembl HapMap |
| WRN | Werner syndrome | 8p12 | Finnish, North American, Mexican, Japanese | The 1367 Cys/Arg polymorphism was examined during aging in 175 Finnish centenarians and 178 newborns, 169 Mexican newborns, 23 North American adults and 198 Japanese adults | When newborns and centenarians were compared within the Finnish population no differences were observed in the proportions of 1367 Cys/Arg across age groups. The frequency of the 1367 Arg allele, thought to be protective against myocardial infarction in a Japanese population, was approximately three times higher in the North American and Finnish adult populations. | Castro et al., 1999 | Entrez Gene UniGene Ensembl HapMap |
| WRN | Werner syndrome | 8p12 | Finnish, Mexican | Population studies of the 1074Leu/Phe and 1367Cys/Arg polymorphisms were undertaken to evaluate the role of WRN in atherogenesis | Frequencies of the 1074Leu/Phe polymorphisms revealed an age-dependent decline of 1074Phe/Phe genotype. There was a tendency for the 1074Phe allele to be associated with coronary stenosis in a gene dose-dependent manner. The 1367Arg/Arg genotype predicted a lower degree of coronary artery occlusion, when compared to the 1367Cys/Cys or 1367Cys/Arg genotypes. However, these tendencies did not achieve statistical significance. | Castro et al., 2000 | Entrez Gene UniGene Ensembl HapMap |
| WRN | Werner syndrome | 8p12 | Dutch, Leiden | The i1-C/T, L1074F and C1367R polymorphisms were examined in 1245 participants aged 85 years and older | The polymorphisms were not found to influence aging-trajectories and survival | Kuningas et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
| XRCC1 | X-ray repair complementing defective repair in Chinese hamster cells 1 | 19q13.31 | English | R194W, R399Q and a [AC]n microsatellite in the 3' UTR polymorphisms were examined in a cohort of newborns (n=290) and a retired population (average age at sampling 70.02 years; n=430) | No evidence of association with longevity was found | Wilding et al., 2006 | Entrez Gene Ensembl HapMap |
| XRCC3 | X-ray repair complementing defective repair in Chinese hamster cells 3 | 14q32.33 | English | T241M and a [AC]n microsatellite in intron 3 polymorphisms were examined in a cohort of newborns (n=290) and a retired population (average age at sampling 70.02 years; n=430) | No evidence of association with longevity was found | Wilding et al., 2006 | Entrez Gene Ensembl HapMap |
| XRCC4 | X-ray repair complementing defective repair in Chinese hamster cells 4 | 5q14.2 | English | I134T polymorphism was examined in a cohort of newborns (n=290) and a retired population (average age at sampling 70.02 years; n=430) | No evidence of association with longevity was found | Wilding et al., 2006 | Entrez Gene Ensembl HapMap |
| XRCC5 | X-ray repair complementing defective repair in Chinese hamster cells 5 | 2q35 | English | [GAPyA]n microsatellite located 120 kb 5' of XRCC5 was examined in a cohort of newborns (n=290) and a retired population (average age at sampling 70.02 years; n=430) | No evidence of association with longevity was found | Wilding et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
| YTHDF2 | YTH domain family, member 2 | 1p35.3 | Italian | A locus associated with human longevity corresponds to a (TG)n microsatellite in the YTHDF2 gene. 412 participants of different ages, including 137 centenarians, were genotyped. | The increased homozygosity in centenarians at this locus was confirmed, and observed a concomitantly increased frequency of the most frequent allele and the corresponding homozygous genotype. The same genotype was associated with increased YTHDF2 messenger RNA levels in immortalized lymphocytes. | Cardelli et al., 2006 | Entrez Gene UniGene Ensembl HapMap |
Please note: Highlighted in yellow are studies that report a statistically significant association between a given gene and human longevity and/or survival in old age. These studies were manually selected after reviewing the literature but the highlight is meant merely as a guide and users are encouraged to consult the relevant reference for additional details.
Updated: 20/06/2007