no it does not but then you do not know genetics do you. DNA causes transsexualism
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402034/
Androgen Receptor Repeat Length Polymorphism Associated with Male-to-Female Transsexualism
Lauren Hare,
Pascal Bernard,
Francisco J. Sánchez,
Paul N. Baird,
Eric Vilain,
Trudy Kennedy, and
Vincent R. Harley
Human Molecular Genetics Laboratory (LH, PB, VRH), Prince Henry's Institute of Medical Research; Department of Genetics (LH, VRH), Monash University; Centre for Eye Research Australia (PNB), University of Melbourne and Royal Victorian Eye and Ear Hospital; Monash Gender Dysphoria Clinic (TK), Moorabbin, Melbourne, Australia; and the Department of Human Genetics (FJS, EV), 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
Abstract
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.
Keywords: Androgen receptor,
AR, aromatase,
CYP19,
ERβ, estrogen receptor β, gender identity disorder, transsexualism
From an early age, people develop an inner sense of being male or female. Transsexuals however, identify with a physical sex opposite to their biological sex. Such individuals might seek to alleviate their distress by altering their bodies through hormone therapy and sex reassignment surgery (
1). The prevalence of transsexualism ranges from 1:2,900 to 1:100,000; and little is known about the etiology of this condition (
2–
4). Some theories have suggested that psychosocial factors— including dysfunctional family dynamics (
5) and traumatic childhood experiences (
6)—lead to the development of a transsexual identity.
Increasingly, biomedical research is implicating biological factors. Co-occurrence among twin pairs, father-son pairs, and brother-sister pairs (
7,
8) raises the question of whether gender dysphoria is heritable. Anatomical studies show that certain brain structures in male-to-female transsexuals are more “female-like” in volume and neuronal density (
9,
10). Furthermore, the response to the odor of male and female steroids in male-to-female transsexuals was more similar to that of control women than control men (
11). Other studies suggest that sex steroids influence gender identity. Female-to-male transsexuality has been associated with polycystic ovary syndrome and hyperandrogenemia (
12). Moreover, female subjects with the disorder of sex development called congenital adrenal hyperplasia are exposed to high levels of androgens prenatally and seem to be at much higher risk of gender identity disorder than the general population (
13). A significant association was identified between female-to-male transsexualism and the
CYP17 gene (which encodes 17α-hydroxylase, the enzyme deficient in some virilized congenital adrenal hyperplasia patients) (
14). Aromatase (
CYP19), the enzyme that converts testosterone to estrogen, has also been implicated in female gender identity. A 46, XX woman with congenital adrenal hyperplasia carried a null
CYP19 mutation, was born with phallic enlargement, a uterus, and ovaries, and exhibited a persistent male gender identity and male gender role behavior (
15).
There are few genetic association studies of male-to-female transsexualism. A study of 29 Swedish male-to-female transsexuals identified a significant association with a dinucleotide CA polymorphism in the estrogen receptor β (
ERβ) gene (
p = .03) (
16). It has been suggested that
ERβ has a defeminization role in male brain and behavior, on the basis of knockout mouse studies (
17). Altogether, genetic studies on transsexuals suggest that both androgen and estrogen might play a role in gender identity.
We sought to investigate whether sex steroidogenesis genes are associated with male-to-female transsexualism in the largest cohort collected to date. We analyzed the variable polymorphism lengths of three genes—
androgen receptor (
AR),
ERβ, and
CYP19—in Caucasian transsexuals and compared these with non-transsexual male control subjects.
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Methods and Materials
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 this study were obtained from MMC and UCLA, and consent procedures adhered to the tenets of the Declaration of Helsinki. The sexuality is only known for approximately 40% of patients, because some patients did not wish to discuss or disclose this information or the patient's sexuality was flexible and not easily classified.
Genotyping
Genomic DNA was extracted from whole blood (
18) or saliva (OrageneT).
Androgen receptor exon 1 CAG repeat was amplified with polymerase chain reaction with VIC-labelled 5′-TCTGGAT-CACTTCGCGCAC-3′ and 5′-GTTCCTCATCCAGGACCAGGTA-3′. The
ERβ intron 5 CA repeat was amplified with FAM-labelled 5′-GGTACAGACCATGGTTTACC-3′, and 5′-AACAAAATGTT-GAATGAGTGGG-3. The
CYP19 intron 4 TTTA repeat was amplified with NED-labelled 5′-GGTACTTAGTTAGCTACAATC-3′, and 5′-GGGTGATAGAGTCAGAGCCT-3′. Polymerase chain re action was 95°C for 30 sec, 30 sec at 59°C for
AR, 55°C for
ERβ, and 58°C for
CYP19, and extension at 72°C for 30 sec for 35 cycles. The polymerase chain reaction products from the three genes were then mixed for each individual with Genescan LIZ-500 size standard and analyzed on an ABI Prism 3130
xl (Applied Biosystems, Foster City, California). Successful genotyping was achieved for at least 101 of the 112 transsexual individuals across the three gene polymorphisms (101 for
AR, 111 for
ERβ, and 104 for
CYP19) and 258 control subjects.
Statistics
To evaluate the repeat length polymorphism data for possible associations with male-to-female transsexualism, independent samples
t tests were used. Interactions between the three gene polymorphisms were evaluated with a binary logistic regression model. Analyses were performed with Statistical Package for the Social Sciences 12.0 software (SPSS, Chicago, Illinois). A
p value < .05 was considered significant. The primary analysis performed was of the association between male-to-female transsexualism and
AR,
ERβ, and
CYP19 genotypes.
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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 control subjects (245.1 base pairs,
p = .04).
