Trade-off in the effect of the APOE gene on the ages at onset of cardiocascular disease and cancer across ages, gender, and human generations.

Abstract:

:Decades of studies of candidate genes show their complex role in aging-related traits. We focus on apolipoprotein E e2/3/4 polymorphism and ages at onset of cardiovascular diseases (CVD) and cancer in the parental and offspring generations of the Framingham Heart Study participants to gain insights on the role of age and gender across generations in genetic trade-offs. The analyses show that the apolipoprotein E e4 allele carriers live longer lives without cancer than the non-e4 allele carriers in each generation. The role of the e4 allele in onset of CVD is age- and generation-specific, constituting two modes of sexually dimorphic genetic trade-offs. In offspring, the e4 allele confers risk of CVD primarily in women and can protect against cancer primarily in men of the same age. In the parental generation, genetic trade-off is seen in different age groups, with a protective role of the e4 allele against cancer in older men and its detrimental role in CVD in younger women. The puzzling complexity of genetic mechanisms working in different genders, ages, and environments calls for more detail and systemic analyses beyond those adapted in current large-scale genetic association studies.

journal_name

Rejuvenation Res

journal_title

Rejuvenation research

authors

Kulminski AM,Culminskaya I,Arbeev KG,Ukraintseva SV,Arbeeva L,Yashin AI

doi

10.1089/rej.2012.1362

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

28-34

issue

1

eissn

1549-1684

issn

1557-8577

journal_volume

16

pub_type

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