Transsexualität, Androgenrezeptoren und Gene

Hier noch einmal ein paar Studien zur Transsexualität:

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 beta (ERbeta), 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 ERbeta 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 ERbeta 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.

Quelle: Androgen receptor repeat length polymorphism associated with male-to-female transsexualism

Die Forschung zeigt, dass Transsexualität eine genetische Komponente hat. Bestimmte Gene sorgen dafür, dass die Androgenrezeptoren weniger empfindlich sind. Ein rein spekulativer Vorteil wäre dann, dass Frauen mit diesem Gen als schöner wahrgenommen werden würden und insoweit bessere Fortpflanzungsfähigkeiten hätten.

Eine weitere Studie drückt sich sehr vorsichtig aus, geht aber in die gleiche Richtung:

Transsexualism is characterised by lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and–after aromatase-catalyzed conversion to estradiol–via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ERbeta gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy male controls. Transsexuals differed from controls with respect to the mean length of the ERbeta repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.

Quelle: Sex steroid-related genes and male-to-female transsexualism.

Eine andere Studie untersucht die Anzahl weiblicher Verwandten bei Transsexuellen:

A significant skewing in the sex ratio in favour of females has been reported for the families of homosexual men such that there are fewer maternal uncles than aunts. This finding is repeated for a large series of transsexual families in this study. Four hundred and seventeen male-to-female transsexuals and 96 female-to-male transsexuals were assessed. Male-to-female transsexuals have a significant excess of maternal aunts vs. uncles. No differences from the expected parity were found for female-to-male transsexuals or on the paternal side. A posited explanation for these findings invokes X inactivation and genes on the X chromosome that escape inactivation but may be imprinted. Our hypothesis incorporates the known familial traits in the families of homosexuals and transsexuals by way of retention of the grand parental epigenotype on the X chromosome. Generation one would be characterized by a failure to erase the paternal imprints on the paternal X chromosome. Daughters of this second generation would produce sons that are XpY and XmY. Since XpY expresses Xist, the X chromosome is silenced and half of the sons are lost at the earliest stages of pregnancy because of the normal requirement for paternal X expression in extra-embryonic tissues. Females survive by virtue of inheriting two X chromosomes, and therefore the possibility of X chromosome counting and choice during embryonic development. In generation three, sons inheriting the paternal X after its second passage through the female germline survive, but half would inherit the feminizing Xp imprinted genes. These genes could pre-dispose the sons to feminization and subsequent development of either homosexuality or transsexualism.

Quelle: The disparate maternal aunt-uncle ratio in male transsexuals: an explanation invoking genomic imprinting

Imprinting bedeutet, dass nur das Gen der Mutter oder des Vaters aktiv wird, dass andere Gen wird unterdrückt (das dies bei einigen Gene vorliegt, und zwar wechselseitig, war eine der Probleme des Klonens). Es ist insoweit eine interessante Theorie, die auch wieder genetische Vorteile darlegen könnte.

Interessant auch eine Studie zur regionalen Verteilung der 5-alpha-reductase deficiency, bei der die Betroffenen intersexuell sind, aber weibliche äußere Geschlechtsorgane haben und deswegen häufig als Frauen erzogen werden, auch wenn sie häufig ein männliches Gehirngeschlecht haben.

Knowledge of steroid 5 alpha-reductase type 2 (SRD5A2) gene mutations is expanding, and its role has been implicated in various disease susceptibilities concerning reproductive health. Extensive research has revealed the tendency for specific SRD5A2 gene mutations to be passed along certain racial, ethnic and geographically isolated groups, which suggests population specificity of these mutations. The review provides evidence of variation in the mutational spectrum of the SRD5A2 gene leading to population-specific high prevalence of characteristic disease or phenotypic expression.

Quelle: SRD5A2 gene mutations–a population-based review

Was dann auch erklärt, warum in bestimmten Populationen Transsexualität oder Intersexualität  eine andere Bedeutung hat