Abstract

Transsexualism is characterized by a marked incongruence between one’s experienced gender and biological sex (1). Transsexuals are individuals who seek, or have undergone, a social transition from male-to-female (MtF) or female-to-male (FtM) (2). A review of the literature has shown that concordance is higher in monozygotic than in dizygotic twins (3), suggesting a genetic contribution to transsexualism. Aim: To analyze the polymorphisms rs3138774, rs2234693, rs743572, rs9340799, rs113770630, rs193922933, and rs60271534 in a transsexual MtF and FtM sample provide by the Gender Units from the Clínic Hospital (Barcelona) and Carlos Haya Hospital (Málaga), Material and Methods: The polymorphisms were analyzed following the previously outlined protocols (4–6). The analyses were performed using the SNPStats software (7). Also a backward stepwise cross-interaction analysis was performed. False positives were controlled with the Bonferroni correction. Results: We found an association by the estrogen receptor (ER) α-β with transsexualism in the FtM population (4, 8, 9). With respect to ERβ, FtMs showed a higher number of CA repeats than the control population, associated to a strong susceptibility to transsexualism (4). The ERα was also implicated (9). However, the rs743572 and rs60271534 polymorphisms were not (4, 8, 10, 11). Using the software SNPStats we found that specific polymorphic allele combinations of ERα, ERβ and AR are involved in MtFs, and that MtFs gender development requires AR, which must be accompanied by ERβ. Conclusion: Our data show that ERs play a key role in the typical human brain differentiation.