Association of the (CA)n Polymorphism of the Estrogen Receptor Gene ESR2 with Gender Incongruence in a Female Sample of Patients in Russia

Abstract The etiology and pathogenesis of gender dysphoria (GD) remain unclear. Psychosocial theories put forward at the end of the last century have not received empirical support. Studies of monozygotic twin pairs concordant for gender dysphoria suggest that GD is largely (23 to 33%) determined by genetic factors. Previously, variations in candidate genes involved in the hormonal regulation system were investigated in search of a genetic component of GD. Specifically, conflicting data were obtained in different samples of individuals with GD regarding the association of variants in the androgen receptor (AR) and estrogen receptor (ESR2) genes, as well as the aromatase gene (CYP19A1), with the development of transsexualism. Studies of female samples of patients with gender incongruence at the genetic level are extremely limited worldwide. Similar studies have not yet been conducted on a sample in Russia. The objective of this study was to investigate polymorphisms in the AR, ESR2, and CYP19A1 gene loci in a sample of female patients in Russia diagnosed with transsexualism and to identify associations between the disorder and genetic polymorphism. The study included women with congenital irreversible gender identity disorders (n = 251) with varying degrees of clinical severity of transsexualism (nuclear, transitional, and marginal forms) and a control group without gender identity disorders (n = 148). No statistically significant associations were found between transsexualism and AR and CYP19A1 gene polymorphisms, which is consistent with previously published studies. However, statistically significant differences in allele and genotype frequencies were found for the ESR2 gene locus between these groups.