Abstract

Aim: To investigate the implication of the estrogen receptor α gene promoter region in the etiology of Gender Dysphoria (GD). Methods: Four polymorphisms (rs3138774, rs9478245, rs2234693 & rs9340799) in the ESR1 promoter were studied from 398 female to males (FtMs), 505 male to females (MtFs), and 1184 controls. They were diagnosed with GD (DSM- 5) by the Gender Identity Units of Cataluña and Andalucía. The controls were diagnosed as not having GD and matched for chromosomal sex, ethnicity and geographical origin. Molecular Analysis: Polymorphisms were amplified by PCR. The rs3138774 was performed by automated capillary electrophoresis. In the case of the other polymorphisms, genotyping was performed by the overnight digestion with the corresponding digestion enzyme (BsrDI, PuvII or XbaI). Statistical methods: The analyses were performed using SNPStats considering p≤.05 as significant. Results: The allele and genotype frequencies for the rs9340799 polymorphism were significantly different between FtMs vs female controls (p=.03 and p=.04) but not between MtFs vs male controls. The A/G genotype showed a protective effect against cerebral masculinization (p=.017) while the A/A genotype is a risk factor (p=.011). No significant differences were found for the other polymorphisms. Conclusion: The ERα rs9340799 polymorphism is implicated in the etiology of GD.