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

ABSTRACT: Apolipoprotein E (APOE) gene has been the most replicated longevity-associated gene in humans. Two common APOE alleles are either significantly depleted (?4 allele) or enriched (?2 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 ?2 allele (p=0.003) and ?2/?3 genotype (p=0.005), and significant depletion of ?3/?4 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.

SUBMITTER: Ryu S

PROVIDER: S-EPMC4818712 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Ryu Seungjin S Atzmon Gil G Barzilai Nir N Raghavachari Nalini N Suh Yousin Y

Mechanisms of ageing and development 20160227

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 significa ...[more]

PMID: 26930295

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

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

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