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Sex Differences in the Association of Apolipoprotein E and Angiotensin-Converting Enzyme Gene Polymorphisms With Healthy Aging and Longevity: A Population-Based Study From Southern Italy

¹ Laboratory of Geriatrics and Gerontology, Research Department, and ² Geriatric Unit, Medical Sciences Department, IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo (FG), Italy.
³ Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Italy.
⁴ Care of the Elderly, Department of Clinical Science at North Bristol, University of Bristol, United Kingdom.
⁵ Laboratory of Hemostasis and Thrombosis, Research Department, IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo (FG), Italy.
⁶ Department of Clinical and Experimental Medicine, "Federico II" University, Naples, Italy.
⁷ Research Department, IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo (FG), Italy.
⁸ CSS-Mendel Institute, Rome, Italy.

Address correspondence to Davide Seripa, PhD, Laboratory of Geriatrics and Gerontology, Research Department c/o Poliambulatorio "Giovanni Paolo II," IRCCS "Casa Sollievo della Sofferenza," Viale Cappuccini, San Giovanni Rotondo (FG), I-71013. E-mail: dseripa{at}operapadrepio.it

We investigated the association of sex and age with the occurrence of apolipoprotein E (apoE) and angiotensin-converting enzyme (ACE) genotypes in healthy aging and longevity in 1344 healthy individuals and 64 centenarians. As compared to participants younger than 60 years, a significant higher frequency of the apoE/2 was observed in men aged 60–90 years (p <.001) and in centenarians (p <.001). Logistic regression analysis confirmed this outcome in both participants aged 60–90 years (odds ratio [OR] = 1.897; 95% confidence interval [CI], 1.227–2.931) and centenarians (OR = 3.263; 95% CI, 1.860–5.722). A further significant association of ACE/D allele and age was observed in centenarians (OR = 2.135; 95% CI, 1.253–3.636). Heterosis was also observed at the ACE locus. No relationship between apoE and ACE polymorphism was found. These findings suggest a role of sex in the association of apoE and ACE gene polymorphisms with healthy aging and longevity.