Androgen Receptor Repeat Length Polymorphism Associated with Male-to-Female Transsexualism
Received 15 April 2008; received in revised form 13 August 2008; accepted 25 August 2008. published online 30 October 2008.
Background
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.
Methods
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.
Results
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.
Conclusions
This study provides evidence that male gender identity might be partly mediated through the androgen receptor.
aHuman Molecular Genetics Laboratory, Prince Henry's Institute of Medical Research, Melbourne, Australia
bDepartment of Genetics, Monash University, Melbourne, Australia
cCentre for Eye Research Australia, University of Melbourne and Royal Victorian Eye and Ear Hospital, Melbourne, Australia
dMonash Gender Dysphoria Clinic, Moorabbin, Melbourne, Australia
eDepartment of Human Genetics, University of California, Los Angeles, California
Address reprint requests to Vincent R. Harley, BSc(PhD), Human Molecular Genetics Laboratory, Prince Henry's Institute of Medical Research, Melbourne, Australia
ABSTRACT