Estudio genómico de la incongruencia de género mediante la tecnología de microarrays

Zusammenfassung

Gender incongruence is defined in the ICD-11 (World Health Organization, 2018) as a marked and persistent disagreement between the experienced gender and the assigned natal sex. Its origin is complex and multifactorial. Objective: The main objective was focused on the analysis of different DNA polymorphisms in a transgender population in contrast to a cisgender population. The first part of the investigation involved the analysis of four polymorphisms that are encoded in the promoter of the estrogen receptor alpha (ESR1) gene. The second part focused on the study of 247 polymorphisms situated in the coactivator molecules NCoA-1, NCoA-2, NCoA-3, NCoA-4, NCoA-5 and p300-CREBBP given the close relationship between steroids and coactivators of steroids. Finally, 242 polymorphisms located in the mitochondrial DNA and their relationship with gender incongruence were analyzed, given the total absence of research related to this topic. Material and methods: In all polymorphisms, allele and genotypic frequencies were analyzed using the χ2 test, comparing the cis- and transgender populations with respect to their natal sex. The strength of association of each polymorphism with gender incongruence was measured using binary logistic regression. Regarding the only repeated polymorphism analyzed (C2), the number of repetitions was analyzed with the Mann- Whitney U test. Linkage disequilibrium and haplotype frequency analyses were also performed. Results: Regarding the ESR1 gene, it was found that the mean of repetitions for the C2 polymorphism was smaller in the transgender men population than in the cisgender population. The S/S and S/L genotypes were overrepresented in the transgender men population (P<0.012 and P<0.003 respectively). An overrepresentation of the A/A genotype was also found for the C4 polymorphism in the transgender men population (P<0.017), while the A/G was overrepresented in the cisgender population (P<0.009]. Regarding the study of cofactor molecules, significant differences were found in eleven polymorphisms located in NCoA-1, NCoA-2, and p300-CREBBP. Coactivators NCoA-2 and p300-CREBBP being those with the highest number of polymorphisms with statistical significance (5/64 and 2/9 respectively). Furthermore, only polymorphisms P2 (located in NCoA-1), P9 and P10 (located in p300-CREBBP) showed different genotypic distribution depending on the covariate “sex”. Regarding mitochondrial polymorphisms, significant differences (P<0.05) were found in 26 polymorphisms; only one of them passed the Bonferroni correction (P<0.0002), being linked to the MT-ND4 and MT-ND5 genes, with an OR=17.33. Conclusion: The ESR1, NCoA-1, NCoA-2, p300-CREBBP, MT-ND4 and MT-ND5 genes can be considered to be involved in gender incongruence