Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study.

Journal Article (Journal Article)

The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Family Study, and intermediate mechanisms, which can link this allele with age-related phenotypes. We focused on age-related macular degeneration, bronchitis, asthma, pneumonia, stroke, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, diseases of heart (HD), cancer, and survival. Our analysis detected favorable associations of the ε2 allele with lower LDL-C levels, lower risks of HD, and better survival. The ε2 allele was associated with LDL-C in each gender and biodemographic cohort, including long-living individuals, offspring, and spouses, resulting in highly significant association in the entire sample (β = -7.1, p = 6.6 × 10-44 ). This allele was significantly associated with HD in long-living individuals and offspring (relative risk [RR] = 0.60, p = 3.1 × 10-6 ) but this association was not mediated by LDL-C. The protective effect on survival was specific for long-living women but it was not explained by LDL-C and HD in the adjusted model (RR = 0.70, p = 2.1 × 10-2 ). These results show that ε2 allele may favorably influence LDL-C, HD, and survival through three mechanisms. Two of them (HD- and survival-related) are pronounced in the long-living parents and their offspring; the survival-related mechanism is also sensitive to gender. The LDL-C-related mechanism appears to be independent of these factors. Insights into mechanisms linking ε2 allele with age-related phenotypes given biodemographic structure of the population studied may benefit translation of genetic discoveries to health care and personalized medicine.

Full Text

Duke Authors

Cited Authors

  • Kulminski, AM; Raghavachari, N; Arbeev, KG; Culminskaya, I; Arbeeva, L; Wu, D; Ukraintseva, SV; Christensen, K; Yashin, AI

Published Date

  • November 2016

Published In

Volume / Issue

  • 17 / 5-6

Start / End Page

  • 893 - 905

PubMed ID

  • 27447179

Pubmed Central ID

  • PMC5065761

Electronic International Standard Serial Number (EISSN)

  • 1573-6768

International Standard Serial Number (ISSN)

  • 1389-5729

Digital Object Identifier (DOI)

  • 10.1007/s10522-016-9659-3


  • eng