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Liu L.N.,CAS Kunming Institute of Zoology | Wang C.Y.,Chinese Academy of Forestry | Lu X.,CAS Kunming Institute of Zoology | Xiao F.H.,CAS Kunming Institute of Zoology | And 4 more authors.
Science China Life Sciences | Year: 2014

MNS16A, a variable number of tandem repeats polymorphism in the TERT gene, has been suggested to regulate telomerase activity. As telomerase activity has been reported to be related to life-span, we hypothesized that this polymorphism might affect human longevity by controlling the length of the telomere. To test this hypothesis, we collected 446 unrelated pericentenarian individuals (age⩾90, mean 94.45±3.45 years) and 332 normal controls (age 22–53, mean 35.0±12.0 years) from Dujiangyan, Sichuan, China. We typed the MNS16A polymorphism in both groups, and compared the allele and genotype frequencies between the peri-centenarian and control groups using the chi-squared test. There was no significant difference between the peri-centenarian and control groups. Thus, the MNS16A polymorphism in TERT might not influence human life-span, at least in the Han Chinese population studied here. © 2014, The Author(s). Source

He Y.-H.,CAS Kunming Institute of Zoology | He Y.-H.,KIZ CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases | Lu X.,CAS Kunming Institute of Zoology | Lu X.,KIZ CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases | And 6 more authors.
Meta Gene | Year: 2014

Aim: Genetic factors play important roles in determining human lifespan. Although some "longevity genes" have been identified to be implicated in human longevity, many disease-associated variants were also observed in the long-lived individuals. The oldest old and their offspring usually have a lower prevalence of age-related diseases, which is likely attributed to a reduction or an absence of disease risk variants. Methods and results: To test this hypothesis, 23 disease risk single nucleotide polymorphisms (SNPs), identified by previous genome-wide association studies (GWASs), were selected and genotyped in 1074 samples consisting of 574 longevity subjects (over 90. years old) and 500 younger controls. Our results revealed that 5 SNPs (rs2144300, rs1864163, rs2200733, rs1967017, and rs7193343) displayed significantly lower allelic frequencies and odds ratios (ORs) in the longevity group than that in the control group. The frequencies of homozygous mutation genotypes and corresponding ORs of the rs1864163, rs2200733, rs127430, rs1967017, and rs12413409 were lower in the longevity subjects. Interestingly, most of the abovementioned SNPs convey susceptibility to cardiovascular disease (CVD), which is the leading cause of deaths in old adults but shows a much lower incidence in the longevity individuals and their offspring. Conclusion: Taking into account the observation that the longevity subjects and their offspring have lower rate of cardiovascular mortality, it is then most plausible that the lack of disease risk variants, especially the CVD, is a genetic contributor to longevity in the Chinese population. © 2014. Source

Liu Y.-W.,CAS Kunming Institute of Zoology | Liu Y.-W.,KIZ CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases | Liu Y.-W.,University of Chinese Academy of Sciences | He Y.-H.,CAS Kunming Institute of Zoology | And 8 more authors.
Neurobiology of Aging | Year: 2014

A673T, a rare variant in the amyloid-β precursor protein gene, shows a protective potential against Alzheimer's disease (AD) and age-related cognitive decline in an Icelandic population. Although A673T was observed independently in a Finnish population, this variant was absent in 8721 Asian subjects. The conflicting observations suggest that the contribution of A673T may be confined to Europeans and Americans rather than Asians. Nevertheless, A673T confers a protective function against AD and thus may be observed only in longevity subjects; thus it is not surprising to see its absence when the general populations or the patient cohorts were considered. To test whether the A673T contributes to the Chinese population, 1237 healthy longevity subjects (mean age 96.9 years) and 1404 matched younger controls (mean age 44.2 years) were genotyped for the variant. Our study failed to observe this variant in either the longevity subjects or the controls. Given the previous observation from Asians, our results suggest that the A673T variant is not involved in longevity in Chinese individuals; some other protective mechanisms may contribute to a lower incidence of AD in Chinese nonagenerians and centenarians. © 2014 Elsevier Inc.. Source

Yang J.-K.,Yunnan University | Gong Y.-Y.,CAS Kunming Institute of Zoology | Xie L.,CAS Kunming Institute of Zoology | Yang Y.,CAS Kunming Institute of Zoology | And 3 more authors.
Molecular Biology Reports | Year: 2014

The cholesteryl ester transfer protein (CETP), which is involved in the regulation of reverse cholesterol transport and metabolism of high-density lipoprotein cholesterol, has been proposed as a candidate gene for human longevity. SNPs in the promoter region of the CETP gene is likely important in regulation of the expression of the CETP gene. To explore the potential effects of the promoter polymorphisms in the CETP gene on longevity, we investigated the promoter polymorphisms in a sample of long-lived (≥90 years old) Han Chinese collected from Southwestern China (N = 380). By resequencing 934 bp of the promoter region, genotypes of four SNPs (-573A/G, -629A/C, -971A/G, -1046T/C) were examined in this sample. However, no association could be confirmed between longevity and these SNPs or haplotypes inferred from them. A novel rare variant -573A/G was found and was found in heterozygote state only in five persons in the Longevity group. But it was not statistically significant (p = 0.075). We also examined this novel polymorphism -573A/G in another Han Chinese sample from Yunnan province, and it was not associated with longevity. The results from both samples suggest that there is likely no association of the CETP gene promoter polymorphisms with longevity, at least among Han Chinese. © 2013 Springer Science+Business Media Dordrecht. Source

He Y.-H.,CAS Kunming Institute of Zoology | He Y.-H.,Joint Laboratory of Bioresources and Molecular Research in Common Diseases | Lu X.,CAS Kunming Institute of Zoology | Lu X.,Joint Laboratory of Bioresources and Molecular Research in Common Diseases | And 5 more authors.
Aging | Year: 2014

Human lifespan is determined greatly by genetic factors and some investigations have identified putative genes implicated in human longevity. Although some genetic loci have been associated with longevity, most of them are difficult to replicate due to ethnic differences. In this study, we analyzed the association of 18 reported gene single nucleotide polymorphisms (SNPs) with longevity in 1075 samples consisting of 567 nonagenarians/centenarians and 508 younger controls using the GenomeLab SNPstream Genotyping System. Our results confirm the association of the forkhead box O3 (FOXO3) variant (rs13217795) and the ATM serine/threonine kinase (ATM) variant (rs189037) genotypes with longevity (p=0.0075 and p=0.026, using the codominant model and recessive model, respectively). Of note is that we first revealed the association of insulin-like growth factor binding protein 3 (IGFBP-3) gene polymorphism rs11977526 with longevity in Chinese nonagenarians/centenarians (p=0.033 using the dominant model and p=0.035 using the overdominant model). The FOXO3 and IGFBP-3 form important parts of the insulin/insulin-like growth factor-1 signaling pathway (IGF-1) implicated in human longevity, and the ATM gene is involved in sensing DNA damage and reducing oxidative stress, therefore our results highlight the important roles of insulin pathway and oxidative stress in the longevity in the Chinese population. © He et al. Source

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