Gender dysphoria is a mental state characterized by a conflict between a person's genetic sex and his/her gender perception. Gender dysphoria comprises several different entities, among them transvestism, cross-dressing, and transsexualism. The Diagnostic and Statistical Manual of Mental Disorders defines transsexualism as the desire to be of the opposite sex or the assertion that one is of the sex opposite from the one assigned at birth. It is a rare condition, with incidence rates between 1:12,000 to 1:40,000.Point of Order, Mr Speaker! Recent data indicates between 1 in 3000 and 1 in 12000. To continue:
The etiology of transsexualism is unknown, but it has been speculated that the influence of sex steroids on early brain development may play an important role. Transsexualism may also have a genetic component, based on rare reports of twin–twin concordance and families with several affected members. Chromosomal aberrations are not found at an increased rate among both male-to-female (MtF) and female-to-male (FtM) transsexuals based on a study in 30 and 31 affected individuals, respectively. In a small series of 29 Swedish MtF transsexuals, however, Henningsson et al. observed an association between MtF transsexualism and a CA repeat polymorphism in the estrogen receptor (ER) beta gene.
CYP17 A2 T>C is a functional single nucleotide polymorphism (SNP) associated with elevated serum and plasma levels of estradiol (E2), progesterone, and testosterone. In a case-control study, we assessed the genotype frequencies of the CYP17 A2 T>C SNP in a series of Caucasian transsexuals and compared these with controls. We hypothesized that the CYP17 A2 T>C SNP is associated with transsexualism and that mutant alleles will therefore be overrepresented among individuals with this condition.
In our patient population of 151 transsexuals, 102 (68%) were MtF and 49 (32%) were FtM, which is in accordance with patterns previously described elsewhere (13). The mean age at presentation of FtM transsexuals was 33.2 (±7.7 SD) years. The mean age of MtF transsexuals was 41.8 (±9.8 SD) years. This is also in accordance with previous reports indicating that the coming out of FtM transsexuals occurs significantly earlier compared to MtF transsexuals (3), (4) and 13 P.T.
Our study found that carriage of the mutant CYP17 −34 T>C C allele is statistically significantly associated with FtM, but not MtF transsexualism. The CYP17 −34 T>C allele distribution was gender-specific among controls. The MtF transsexuals had an allele distribution equivalent to male controls, whereas the FtM transsexuals did not follow the gender-specific allele distribution of female controls but rather had an allele distribution equivalent to MtF transsexuals and male controls.
We present the largest case-control study of Caucasian transsexuals to date investigating a sex steroid metabolizing gene polymorphism. In this series, the presence of the CYP17 −34 T>C SNP was statistically significantly overrepresented among FtM but not MtF transsexuals, thus supporting CYP17 as a candidate gene of FtM transsexualism.
The article is behind a pay-per view wall, but there's a summary at the New Scientist.