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

Content Provider	Springer Nature Link
Author	Kulminski, Alexander M. Raghavachari, Nalini Arbeev, Konstantin G. Culminskaya, Irina Arbeeva, Liubov Wu, Deqing Ukraintseva, Svetlana V. Christensen, Kaare Yashin, Anatoliy I.
Copyright Year	2016
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.
Starting Page	893
Ending Page	905
Page Count	13
File Format	PDF
ISSN	13895729
Journal	Biogerontology
Volume Number	17
Issue Number	5-6
e-ISSN	15736768
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-07-22
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	ApoE Health span Life span Cell Biology Geriatrics/Gerontology Developmental Biology
Content Type	Text
Resource Type	Article
Subject	Aging Gerontology Geriatrics and Gerontology

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