Apolipoprotein E and familial longevity

NEUROBIOLOGY OF AGING

卷:34

Article

Schupf, Nicole¹  Barral, Sandra¹  Perls, Thomas²  Newman, Anne³  Christensen, Kaare^4,5,6  Thyagarajan, Bharat⁷  Province, Michael⁸  Rossi, Winifred K.⁹  Mayeux, Richard¹ 

[1] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA

[2] Boston Univ, Med Ctr, Geriatr Sect, Boston, MA USA

[3] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA

[4] Univ So Denmark, Danish Aging Res Ctr, Odense, Denmark

[5] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark

[6] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, DK-5000 Odense, Denmark

[7] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

[8] Washington Univ, Sch Med, Div Stat Genom, Data Management Coordinating Ctr, St Louis, MO USA

[9] NIA, Bethesda, MD 20892 USA

关键词: Exceptional longevity;    Familial longevity;    Offspring;    APOE;    TOMM40;   

DOI  :  10.1016/j.neurobiolaging.2012.08.019

来源: Elsevier

【 摘 要 】

Exceptional longevity is associated with substantial heritability. The epsilon 4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the epsilon 2 allele with decreased mortality, although inconsistently. Offspring from long-lived families and spouse controls were recruited at 3 sites in the United States and Denmark. We used generalized estimating equations to compare the likelihood of carrying risk alleles in offspring (n = 2307) and spouse controls (n = 764), adjusting for age, sex, level of education, and family membership. The likelihood of carrying an APOE epsilon 4 allele or a G allele in rs2075650 was lower (odds ratio [OR], 0.75; p = 0.005 and OR, 0.70; p = 0.002) and the likelihood of carrying an APOE epsilon 2 allele was higher (OR, 1.5; p = 0.007) among family members in the offspring generation than among their spouse controls. Our findings support the hypothesis that both reduction in the frequency of the epsilon 4 allele and increase in the frequency of the epsilon 2 allele contribute to longevity. (C) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

Free