To investigate the biological mechanism of gender identity disorder (GID), five candidate sex hormone-related genes, encoding androgen receptor (AR), estrogen receptors alpha (ERalpha) and beta (ERbeta), aromatase (CYP19), and progesterone receptor (PGR) were analyzed by a case-control association study. Subjects were 242 transsexuals (74 male-to-female patients (MTF) and 168 female-to-male patients (FTM)), and 275 healthy age- and geographical origin-matched controls (106 males and 169 females). The distributions of CAG repeat numbers in exon 1 of AR, TA repeat numbers in the promoter region of ERalpha, CA repeat numbers in intron 5 of ERbeta, TTTA repeat numbers in intron 4 of CYP19, and six polymorphisms (rs2008112, rs508653, V660L, H770H, rs572698 and PROGINS) of PGR were analyzed. No significant difference in allelic or genotypic distribution of any gene examined was found between MTFs and control males or between FTMs and control females. The present findings do not provide any evidence that genetic variants of sex hormone-related genes confer individual susceptibility to MTF or FTM transsexualism.Compare and contrast with Androgen Receptor Repeat Length Polymorphism Associated with Male-to-Female Transsexualism by Hare at al in Biol.Psych. Vol65, Issue 1, Pp 93-96, as described rather breathlessly by the popular press :
BackgroundThe results were identical for the CYP19 and ERβ genes. The samples sizes were comparable. But the results appear to differ for the AR gene.
There is a likely genetic component to transsexualism, and genes involved in sex steroidogenesis are good candidates. We explored the specific hypothesis that male-to-female transsexualism is associated with gene variants responsible for undermasculinization and/or feminization. Specifically, we assessed the role of disease-associated repeat length polymorphisms in the androgen receptor (AR), estrogen receptor β (ERβ), and aromatase (CYP19) genes.
Subject-control analysis included 112 male-to-female transsexuals and 258 non-transsexual males. Associations and interactions were investigated between CAG repeat length in the AR gene, CA repeat length in the ERβ gene, and TTTA repeat length in the CYP19 gene and male-to-female transsexualism.
A significant association was identified between transsexualism and the AR allele, with transsexuals having longer AR repeat lengths than non-transsexual male control subjects (p = .04). No associations for transsexualism were evident in repeat lengths for CYP19 or ERβ genes. Individuals were then classified as short or long for each gene polymorphism on the basis of control median polymorphism lengths in order to further elucidate possible combined effects. No interaction associations between the three genes and transsexualism were identified.
This study provides evidence that male gender identity might be partly mediated through the androgen receptor.
Maybe not. One experiment, the one showing no evidence of correlation, examined only exon 1 of the AR gene, the one for which tests are most easily available as it has an association with prostate cancer and certain other conditions. The other appears not to have confined itself to exon 1. If so, then instead of a contradiction that casts doubt on the original findings, we may just have narrowed down the area that could make someone slightly more susceptible to being TS. And it is a slight susceptibility, 10% more likely at most. Again, compare and contrast to exposure to the anti-abortifacient drug DES, an estrogenic (female sex hormone) compound during the first trimester of foetal development. There it's not ~10%, it's ~50,000%.
We can also have greater confidence that neither the CYP19 nor ERβ genes play any role.