Association between ESR1 polymorphisms and second to fourth digit ratio in school-aged children in the Hokkaido Study

The ratio of the lengths of the 2nd and 4th digits (2D:4D) is considered an index of prenatal exposure to androgen. Indeed, androgen receptors have been linked to digit length, but estrogen receptors are rarely investigated in this context. Thus, we investigated the association between estrogen receptor 1 (ESR1) genetic polymorphisms and 2D:4D in school-aged children. The 2D:4D ratios were determined using Vernier calipers from photocopies of palms provided by 1800 children aged 7 years who were enrolled in an ongoing prospective cohort study in Hokkaido, Japan. The children were genotyped using cord blood collected at birth for single nucleotide polymorphisms in ESR1, specifically PvuII (T > C, dbSNP: rs2234693), XbaI (A > G, dbSNP: rs9340799), and rs2077647 (A > G). The association between ESR1 polymorphisms and 2D:4D was assessed by multiple linear regression adjusted for potential cofounding factors. Boys with the GG genotype at rs9340799 had a significantly lower 2D:4D in the right hand than boys with the AA/AG genotype (-0.96% lower, 95% confidence interval: -1.68 to -0.24). However, this association was detected only in boys born to non-smoking mothers. No significant differences were found between rs9340799 polymorphisms and 2D:4D among girls. There was also no link between 2D:4D and polymorphisms at rs2234693 and rs2077647. These data suggest that rs9340799 polymorphisms in ESR1 may contribute to digit length and 2D:4D.