Association of polymorphisms of the estrogen receptor α gene with the age of menarche

Background: The age of menarche may be subject to hereditary influences, but the specific genetic determinants are largely unknown. We evaluated whether the XbaI and PvuII polymorphisms of the estrogen receptor a gene are associated with the age of menarche. Methods: We performed genotyping for XbaI and PvuII in a cohort of 145 adolescent females from a closed community in North-Western Greece. Results: There was strong linkage disequilibrium between the two polymorphisms. Menarche occurred later in girls with the XX genotype than in girls with the Xx or xx genotype (mean +/- SD: 13.36+/-1.24 versus 12.80+/-1.14 and 12.75+/-1.35 years respectively; P=0.017). Menarche also tended to occur later in PP homozygotes than in Pp and pp subjects, but the difference was not significant (mean +/- SD: 13.09+/-1.29 versus 12.80+/-1.19 and 12.85+/-1.33 years respectively). The strongest effect was seen when the PX haplotype was considered [mean +/- SD: 13.43+/-1.18 years for homozygotes versus 12.76+/-1.25 years in heterozygotes and in subjects without the PX allele, P=0.006]. Conclusions: We document that the XbaI polymorphism, and possibly PvuII, may be genetic determinants of the age of menarche.