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

dc.contributor.author

Kulminski, Alexander M

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Raghavachari, Nalini

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Arbeev, Konstantin G

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Culminskaya, Irina

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Arbeeva, Liubov

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Wu, Deqing

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Ukraintseva, Svetlana V

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Christensen, Kaare

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Yashin, Anatoliy I

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Netherlands

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2017-06-02T17:28:15Z

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2017-06-02T17:28:15Z

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2016-11

dc.description.abstract

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.

dc.identifier

https://www.ncbi.nlm.nih.gov/pubmed/27447179

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10.1007/s10522-016-9659-3

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1573-6768

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https://hdl.handle.net/10161/14754

dc.language

eng

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Springer Science and Business Media LLC

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Biogerontology

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10.1007/s10522-016-9659-3

dc.subject

ApoE

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Health span

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Life span

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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.

dc.type

Journal article

duke.contributor.orcid

Arbeev, Konstantin G|0000-0002-4195-7832

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/27447179

pubs.begin-page

893

pubs.end-page

905

pubs.issue

5-6

pubs.organisational-group

Center for Population Health & Aging

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Duke

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Duke Population Research Institute

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Institutes and Provost's Academic Units

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Sanford School of Public Policy

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Social Science Research Institute

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Staff

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University Institutes and Centers

pubs.publication-status

Published

pubs.volume

17

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