Polymorphisms of estrogen metabolism genes and longevity: a follow-up study in the Italian population.

Aromatase (CYP19) and estrogen receptor-alpha (ESR1) are both involved in estrogen metabolism. Aromatase catalyzes a critical reaction for estrogen biosinthesis from androgens, and estrogen receptor-alpha mediates the biological action of estrogens. Recent findings have revealed that estrogens have a relevant role not only in female but also in male ageing. In the present paper we investigated the possible association of ESR1 ( PvuII, rs2234693) and CYP19 (rs4646) polymorphisms with longevity by means of a follow-up study. The study population consisted of 258 individuals (43.3% males) born in 1900-1930, who were living in the district of Salerno (Southern Italy) in the year 2000. The mortality information of these subjects was collected in the year 2009. Using the mortality data the sample was divided into two groups of subjects surviving over 90 years (≥ 90yrs) or not. The analysis of ESR1 and CYP19 genotype distribution revealed an excess of homozygotes ESR1 PP (0.30 vs 0.19) and genotypes carrying CYP19 T allele (0.69 vs 0.55) in long-lived subjects compared to non survivors. The logistic regression analysis showed that, after adjusting for sex, both ESR1 and CYP19 genotypes were independently associated with survival over 90 years with OR= 2.20 (C.I.95% 1.04-4.59, p = 0.03) and 1.92 (C.I.95% 1.04-3.55, p = 0.03) respectively. Present findings highlight that estrogen metabolism genes are not only involved in reproduction, but also in ageing and exert a pleiotropic action across the whole human life course.