The genetic basis of the relationship between reproduction and longevity : a study on common variants of three genes in steroid hormone metabolism (CYP17, HSD17B1, COMT).

Evolutionary theories of aging predict an antagonistic relationship between fertility and lifespan in humans, but the genetic basis of this phenomenon is not clear. The variation of three genes in steroid hormone metabolism, CYP17 (rs743572), HSD17B1 (rs 605059) and COMT (rs4680), was examined to elucidate the genetic basis of the relationship between fertility and lifespan. A sample of 277 individuals (mean age, 82.9 years) was recruited in 2000. Based on mortality data collected in 2009, the sample was divided into two groups of subjects surviving to over 90 years (long-lived) or not (controls). Fertility data (number of children) were collected in the same sample. The HSD17B1AA genotype was found to be significantly associated (p=0.0085) with longevity only in the females (estimated odds ratio = 3.77). As the HSD17B1AA genotype was also associated with a higher number of children (5.3±2.1) than the other genotypes (p= 0.006), we may infer that HSD17B1 genotypes could exert a positive pleiotropic action on longevity and fertility. CYP17 and COMT gene variation did not influence either lifespan or fertility. We then searched the literature for genes studied in relation to both reproduction and aging. A review of the studies showed a pleiotropic action for six out of sixteen genes and revealed that genes may exert positive, or negative, or antagonistic pleiotropic actions. These potential actions may be modified by such environmental factors such as changing reproductive behaviors, which seem to be able to mitigate or enhance the a gene's phenotypic effects.