Genetic variants in PVRL2-TOMM40-APOE region are associated with human longevity in a Han Chinese population.

Authors: Lu F; Guan H; Gong B; Liu X; Zhu R; Wang Y; Qian J; Zhou T; Lan X; Wang P; Lin Y; Ma S; Lin H; Zhu X; Chen R; Zhu X; Shi Y; Yang Z

Abstract: PURPOSE: Human longevity results from a number of factors, including genetic background, favorable environmental, social factors and chance. In this study, we aimed to elucidate the association of human longevity with genetic variations in several major candidate genes in a Han Chinese population. METHODS: A case-control association study of 1015 long-lived individuals (aged 90 years or older) and 1725 younger controls (30-70 years old) was undertaken. Rs2075650 in TOMM40 was firstly genotyped using the ABI SNaPshot method in an initial cohort consisted of 597 unrelated long-lived individuals and 1275 younger controls enrolled from Sichuan. Secondly, eighteen tag single-nucleotide polymorphisms (SNPs) in the PVRL2-TOMM40-APOE locus were genotyped for extensive study in the same cohort. Finally, 5 associated SNPs were genotyped in a replication cohort including 418 older individuals and 450 younger controls. The genotype and allele frequencies were evaluated using the chi2 tests. The linkage disequilibrium (LD) block structure was examined using the program Haploview. RESULTS: The case-control study of rs2075650 in TOMM40 showed significant difference in allele frequencies between cases and controls (P = 0.006) in an initial study. Of the 18 SNPs genotyped, rs405509 in APOE and another three SNPs (rs12978931, rs519825 and rs395908) in the PVRL2 gene also showed significant association with human longevity in extensive study in the same cohort. Rs2075650 in TOMM40, rs405509 in APOE and rs519825 in PVRL2 showed a significant association with human longevity in a replication cohort. CONCLUSION: These results suggested that PVRL2, TOMM40 and APOE might be associated with human longevity. However, further research is needed to identify the causal variants and determine which of these genes are involved in the progress of human longevity.

Journal: PloS one
Volume: 9
Issue: 6
Pages: e99580
Date: June 14, 2014
PMID: 24924924
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Citation:

Lu F, Guan H, Gong B, Liu X, Zhu R, Wang Y, Qian J, Zhou T, Lan X, Wang P, Lin Y, Ma S, Lin H, Zhu X, Chen R, Zhu X, Shi Y, Yang Z (2014) Genetic variants in PVRL2-TOMM40-APOE region are associated with human longevity in a Han Chinese population. PloS one 9: e99580.


Longevity Variant Associations (p-value):
  • rs12978931 (0.0445)
  • rs519825 (0.01577)
  • rs419010 (0.091)
  • rs4803766 (0.708)
  • rs11879589 (0.07601)
  • rs395908 (0.048)
  • rs519113 (0.3734)
  • rs6857 (0.518)
  • rs10119 (0.914)
  • rs449647 (0.767)
  • rs405509 (0.027)
  • rs440446 (0.509)
  • rs769448 (0.66)
  • rs769449 (0.62)
  • rs7412 (0.405)
  • rs429538 (0.2821)
  • rs4420638 (0.176)
  • rs2075650 (0.006)

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