Vulnerabilidad Genética de la Transexualidadanálisis de una población española

Abstract

Transsexualism is characterized by a marked incongruence between one’s experienced gender and biological sex. Transsexuals are individuals who seek, or have undergone, a social transition from male-to-female (MtF) or female-to-male (FtM). A review of the literature has shown that concordance is higher in monozygotic than in dizygotic twins, suggesting a genetic contribution to transsexualism. Aim: The first part of the research focused on the cytogenetic and molecular analysis of the karyotype in a transsexual population. The second part of the research focused on the molecular analysis of four short tandem repeat polymorphisms (STRs): ERα-rs3138774, ERβ-rs113770630, AR-rs193922933 and CYP19-rs60271534, and three single nucleotide polymorphisms (SNPs): ERα-rs2234693, ERα-rs9340799 and CYP17-rs743572, in a population of 974 transsexuals and 1327 controls recruited by the Gender Units from the Clínic Hospital (Barcelona) and Carlos Haya Hospital (Málaga). Material and Methods: The karyotype was analyzed using G-banding and a high-density array (Affymetrix CytoScan™). Enzymatic digestion was used for one base polymorphisms (SNPs), and capillary electrophoresis (3130 XL Genetic Analyzer) for repeat polymorphisms. The frequency analyses were performed using Mann-Whitney or Chi-square tests and the software SPSS® 23.0. In addition, a backward stepwise crossinteraction analysis was performed by the software SNPStats. False positives were controlled with the Bonferroni correction. Results: We found an association of the estrogen receptors alpha and beta with transsexualism. With respect to ERβ-rs113770630, FtMs showed a higher number of CA repeats than the control population, associated to a strong susceptibility to transsexualism. We also found an over transmission of the allele A and genotype A/A for ERα-rs9340799 polymorphism in the FtM population. We found that specific allele combinations of ERα- rs9340799, ERβ-rs113770630 and AR-rs193922933 are involved in the MtF population. Conclusion: Our data show that estrogen receptor alpha and beta, play a key role in human brain differentiation.