Brief ReportAndrogen Receptor Repeat Length Polymorphism Associated with Male-to-Female Transsexualism
Section snippets
Participants
One hundred and twelve Caucasian male-to-female transsexuals, pre- and post-operative, were recruited from Monash Medical Centre (MMC), Victoria, Australia (n = 76) and from University of California, Los Angeles (UCLA) (n = 36) as per criteria in the DSM-IV—some of whom had reports of gender dysphoria in childhood. Almost all transsexual individuals were receiving hormone treatment. Two hundred and fifty-eight Caucasian male control subjects were also recruited from MMC. Ethical approvals for
Results
Polymorphic fragment lengths for 258 male subjects and 112 transsexuals were obtained. Twenty-one different alleles were identified for the AR gene polymorphism, 14 for the ERβ gene polymorphism, and 8 for the CYP19 gene polymorphism. The percentages of each allele in the control and transsexual populations are shown in Figure 1. For the AR gene, a difference in the mean repeat length was identified, with transsexuals having significantly longer mean repeat lengths (243.2 base pairs) than
Discussion
To date, this is the largest genetic study of transsexualism conducted. We observed a significant association between longer AR gene polymorphisms and male-to-female transsexualism. Longer CAG repeats in the AR gene lead to reduced binding of the AR protein to co-activator, due to its inhibitory interaction with the receptor, resulting in less effective testosterone signalling (19), a mechanism typically involved in masculinization of the brain during early development (1). Female subjects
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The neurobiology of gender identity and gender dysphoria
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2021, Journal of Sexual MedicineSexual differentiation of the human hypothalamus: Relationship to gender identity and sexual orientation
2021, Handbook of Clinical NeurologyAnalysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence
2020, Sexual MedicineCitation Excerpt :A genetic component may also be involved because siblings of transgender individuals are more likely to be transgender, compared with the general population.11,12 Most genetic studies that analyze the genetic component of gender formation examine the implication of genetic polymorphisms related to the androgen receptor AR,13–18 the aromatase CYP19A1,13–18 the estrogen receptors ER (α and β),13–19 as well as haplotypes and the interaction effects (epistasis) between polymorphisms.20 Estrogen is produced in many regions of the brain including the hippocampus, the cortex, the cerebellum, the hypothalamus, and the amygdala.21