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Genetic landscape of APOE in human longevity revealed by high-throughput sequencing
- Source :
- Mechanisms of Ageing and Development. 155:7-9
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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 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.
- Subjects :
- Male
0301 basic medicine
Apolipoprotein E
Aging
media_common.quotation_subject
Longevity
Regulatory Sequences, Nucleic Acid
Biology
Article
Open Reading Frames
03 medical and health sciences
Exon
Apolipoproteins E
0302 clinical medicine
Genotype
Humans
Allele
Gene
Genotyping
Alleles
media_common
Genetics
High-Throughput Nucleotide Sequencing
030104 developmental biology
Jews
Female
Centenarian
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 00476374
- Volume :
- 155
- Database :
- OpenAIRE
- Journal :
- Mechanisms of Ageing and Development
- Accession number :
- edsair.doi.dedup.....3363315b0a6d949c610aeec9f4abb3cf