Genetic landscape of APOE in human longevity revealed by high-throughput sequencing

Mech Ageing Dev. 2016 Apr:155:7-9. doi: 10.1016/j.mad.2016.02.010. Epub 2016 Feb 27.

Abstract

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 2kb 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.

Keywords: APOE; Centenarian; Genetic variant; Longevity; Pooled target capture sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Apolipoproteins E / genetics*
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Jews
  • Longevity / genetics*
  • Male
  • Open Reading Frames / genetics*
  • Regulatory Sequences, Nucleic Acid / genetics*

Substances

  • Apolipoproteins E