Abstract

Background: Gender Dysphoria (GD) in DSM-5 is characterized by a marked incongruence between one‘s experienced gender and biological sex. The etiology is complex, but some hypotheses suggest that GD arises from discrepant cerebral and genital sexual differentiation due to the interaction of hormone, genetic and environmental factors that contribute to establish gender identity. Aim: To investigate whether ESR1 polymorphism rs9478245 is associated with GD. Methods: Molecular analysis was performed in peripheral blood samples from 29 FtMs (Female to Males), 29 MtF (Male to Females) and 57 sex- and ethnically-matched controls. The rs9478245 polymorphism was analyzed by PCR, generating a 346-bp fragment by the primers 5‘- GATATCCAGGGTTATGTGGCA-3‘ and 5‘-AGGTGTTGCCTATTATATTAACCTTGA-3‘ with a PCR protocol of 94ᵒC 5 min, 45 cycles for 94ᵒC 1 min, 59ᵒC 1 min, 72ᵒC 1 min, and a final extension of 72ᵒC 10 min. Ten microliters of PCR product were digested by restriction enzyme BsrDI 5U (BioLabs, Lawrenceville, GA, USA), incubated overnight at 65ᵒC and visualized in a 6% polyacrylamide gel (GE Healthcare, Barcelona, Spain). Absence of restriction sites was specified as T. The genotypes resulting were C/C, C/T, and T/T. Results: The genotype frequencies for the rs9478245 polymorphism were in Hardy-Weinberg equilibrium (Ttrans=0.97; Ctrans=0.03. Tcontrol=0.99; Ccontrol=0.01). Allele and genotype frequencies were not statistically significant in any group. Genotype association with GD p≤ 0.16 (n=115, adjusted by sex). Interaction analysis with covariate karyotype p≤ 0.28. Conclusions: In spite of the rs9478245 polymorphism disrupting the SRY transcription factor binding site upstream of exon 1 (Weickert et al., 2008), our data showed that this polymorphism is not implicated in the genetic basis of GD.