Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence

INTRODUCTION: Gender incongruence defines a state in which individuals feel discrepancy between the sex assigned at birth and their gender. Some of these people make a social transition from male to female (trans women) or from female to male (trans men). By contrast, the word cisgender describes a person whose gender identity is consistent with their sex assigned at birth. AIM: To analyze the implication of the estrogen receptor α gene (ESR1) in the genetic basis of gender incongruence. MAIN OUTCOME MEASURES: Polymorphisms rs9478245, rs3138774, rs2234693, rs9340799. METHOD: We carried out the analysis of 4 polymorphisms located at the promoter of the ESR1 gene (C1 = rs9478245, C2 = rs3138774, C3 = rs2234693, and C4 = rs9340799) in a population of 273 trans women, 226 trans men, and 537 cis gender controls. For SNP polymorphisms, the allele and genotype frequencies were analyzed by χ(2) test. The strength of the SNP associations with gender incongruence was measured by binary logistic regression. For the STR polymorphism, the mean number of repeats were analyzed by the Mann–Whitney U test. Measurement of linkage disequilibrium and haplotype frequencies were also performed. RESULTS: The C2 median repeats were shorter in the trans men population. Genotypes S/S and S/L for the C2 polymorphism were overrepresented in the trans men group (P = .012 and P = .003 respectively). We also found overtransmission of the A/A genotype (C4) in the trans men population (P = .017), while the A/G genotype (C4) was subrepresented (P = .009]. The analyzed polymorphisms were in linkage disequilibrium. In the trans men population, the T(C1)-L(C2)-C(C3)-A(C4) haplotype was overrepresented (P = .019) while the T(C1)-L(C2)-C(C3)-G(C4) was subrepresented (P = .005). CONCLUSION: The ESR1 is associated with gender incongruence in the trans men population. Fernández R, Delgado-Zayas E,RamírezK, et al. Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence. Sex Med 2020;8:490–500.