ESR2, AR, and CYP19A1 Gene Associations in a Sample of Russian Males with Congenital Irreversible Disorders of Gender Identity

The etiology of transsexualism is still unknown, since this phenomenon has complex causes. Family studies have confirmed that genetic factors play a role in gender-identity disorders. Data were obtained demonstrating association between polymorphisms in hormone regulation system genes, as well as the androgen (AR) and estrogen (ESR2) receptors and aromatase (CYP19A1) genes and transsexualism in different studies. Such studies have not yet been conducted in Russia. The aim of the present work was to investigate genetic association between the AR, ESR2, and CYP19A1 genes and diagnosed transsexualism in a cohort of Russian patients. The study involved male patients with congenital irreversible gender-identity disorders (n = 191) with different degree of clinical severity (“core,” “transitional,” and “marginal”) and the control group of men who did not have gender dysphoria (n = 129). We showed no statistically significant association between transsexualism and the polymorphic variants of the three studied genes, which is consistent with previously published studies. In the group of patients, the frequency of the SS genotypes (containing exclusively alleles with a length less than the median value) of the ESR2 gene (57.07%) and the L genotype (with the length larger than the median value) of the AR gene (53.93%) was higher than in the control group (48.46 and 43.41%, respectively). Also, when only “core” and “transitional” patients were included in the patient group, there was a trend towards a higher level of differences observed compared to the men who did not have gender dysphoria (p = 0.06). The results of this work indirectly confirm the involvement of the androgen receptor in the development of transsexualism. In the future, it would be desirable to expand the range of markers studied for their association with transsexualism, as well as to conduct similar studies in different cohorts.