Apolipoprotein E (APOE) gene has been the most replicated longevity-associated gene in humans. Two common APOE alleles are either significantly depleted (ε4 allele) or enriched (ε2 allele) in long-lived individuals as compared to controls. We performed high-throughput sequencing analysis of exons and 2 kb proximal promoter of APOE in 450 centenarians and 500 controls of Ashkenazi Jewish decent. We found two common regulatory variants, rs405509 (p = 0.006) and rs769449 (p = 0.036), that were significantly depleted in centenarians. Genotyping analysis of rs7412 and rs429358 showed significant enrichment of ε2 allele (p = 0.003) and ε2/ε3 genotype (p = 0.005), and significant depletion of ε3/ε4 genotype (p = 0.005) in centenarians. Our findings support the hypothesis that variants in both coding and regulatory regions of APOE may contribute to longevity in humans.
|Number of pages||3|
|Journal||Mechanisms of Ageing and Development|
|State||Published - 1 Apr 2016|
Bibliographical noteFunding Information:
We would like to thank Archana Tare for critical reading of the manuscript. This work was funded by NIH grants AG024391, AG027734, and AG17242 (Y. S.) and a grant from The Paul F. Glenn Center for the Biology of Human Aging (Y. S.). S. R. is the recipient of a Glenn/AFAR Scholarships for Research in the Biology of Aging.
© 2016 Elsevier Ireland Ltd.
- Genetic variant
- Pooled target capture sequencing
ASJC Scopus subject areas
- Developmental Biology