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

Publication ,  Journal Article
Kulminski, AM; Raghavachari, N; Arbeev, KG; Culminskaya, I; Arbeeva, L; Wu, D; Ukraintseva, SV; Christensen, K; Yashin, AI
Published in: Biogerontology
November 2016

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.

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Published In

Biogerontology

DOI

EISSN

1573-6768

ISSN

1389-5729

Publication Date

November 2016

Volume

17

Issue

5-6

Start / End Page

893 / 905

Related Subject Headings

  • Survival Rate
  • Sex Distribution
  • Risk Factors
  • Quantitative Trait Loci
  • Prevalence
  • Middle Aged
  • Male
  • Longevity
  • Internationality
  • Humans
 

Citation

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MLA
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Kulminski, A. M., Raghavachari, N., Arbeev, K. G., Culminskaya, I., Arbeeva, L., Wu, D., … Yashin, A. I. (2016). Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study. Biogerontology, 17(5–6), 893–905. https://doi.org/10.1007/s10522-016-9659-3
Kulminski, Alexander M., Nalini Raghavachari, Konstantin G. Arbeev, Irina Culminskaya, Liubov Arbeeva, Deqing Wu, Svetlana V. Ukraintseva, Kaare Christensen, and Anatoliy I. Yashin. “Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study.Biogerontology 17, no. 5–6 (November 2016): 893–905. https://doi.org/10.1007/s10522-016-9659-3.
Kulminski AM, Raghavachari N, Arbeev KG, Culminskaya I, Arbeeva L, Wu D, et al. Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study. Biogerontology. 2016 Nov;17(5–6):893–905.
Kulminski, Alexander M., et al. “Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study.Biogerontology, vol. 17, no. 5–6, Nov. 2016, pp. 893–905. Epmc, doi:10.1007/s10522-016-9659-3.
Kulminski AM, Raghavachari N, Arbeev KG, Culminskaya I, Arbeeva L, Wu D, Ukraintseva SV, Christensen K, Yashin AI. Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study. Biogerontology. 2016 Nov;17(5–6):893–905.
Journal cover image

Published In

Biogerontology

DOI

EISSN

1573-6768

ISSN

1389-5729

Publication Date

November 2016

Volume

17

Issue

5-6

Start / End Page

893 / 905

Related Subject Headings

  • Survival Rate
  • Sex Distribution
  • Risk Factors
  • Quantitative Trait Loci
  • Prevalence
  • Middle Aged
  • Male
  • Longevity
  • Internationality
  • Humans