Departamento de Psicología, Universidade da Coruña, A Coruña, Spain.
Departamento de Psicobiología, Universidad Nacional de Educación a Distancia, Madrid, Spain.
Psychoneuroendocrinology. 2018 Dec;98:161-167. doi: 10.1016/j.psyneuen.2018.07.032. Epub 2018 Aug 1.
Polymorphisms in sex steroid receptors have been associated with transsexualism. However, published replication studies have yielded inconsistent findings, possibly because of a limited sample size and/or the heterogeneity of the transsexual population with respect to the onset of dysphoria and sexual orientation. We assessed the role of androgen receptor (AR), estrogen receptors alpha (ERα) and beta (ERβ), and aromatase (CYP19A1) in two large and homogeneous transsexual male-to-female (MtF) and female-to-male (FtM) populations.
The association of each polymorphism with transsexualism was studied with a twofold subject-control analysis: in a homogeneous population of 549 early onset androphilic MtF transsexuals versus 728 male controls, and 425 gynephilic FtMs versus 599 female controls. Associations and interactions were investigated using binary logistic regression.
Our data show that specific allele and genotype combinations of ERβ, ERα and AR are implicated in the genetic basis of transsexualism, and that MtF gender development requires AR, which must be accompanied by ERβ. An inverse allele interaction between ERβ and AR is characteristic of the MtF population: when either of these polymorphisms is short, the other is long. ERβ and ERα are also associated with transsexualism in the FtM population although there was no interaction between the polymorphisms. Our data show that ERβ plays a key role in the typical brain differentiation of humans.
ERβ plays a key role in human gender differentiation in males and females.
性甾体受体的多态性与易性癖有关。然而，已发表的复制研究结果并不一致，这可能是由于样本量有限以及易性癖患者群体在易性癖发作和性取向方面存在异质性。我们评估了雄激素受体（AR）、雌激素受体 alpha（ERα）和 beta（ERβ）以及芳香酶（CYP19A1）在两个大型且同质的易性癖男性转女性（MtF）和女性转男性（FtM）群体中的作用。
通过两倍的病例-对照分析研究了每种多态性与易性癖的相关性：在一个由 549 名早期发病的恋物性 MtF 易性癖患者与 728 名男性对照者、425 名女性恋物性 FtM 患者与 599 名女性对照者组成的同质人群中进行。使用二元逻辑回归分析了关联和相互作用。
我们的数据表明，ERβ、ERα和 AR 的特定等位基因和基因型组合与易性癖的遗传基础有关，MtF 性别发育需要 AR，而 AR 必须与 ERβ 共同存在。ERβ和 AR 之间的反向等位基因相互作用是 MtF 人群的特征：当这些多态性中的任何一个为短型时，另一个则为长型。尽管 ERβ 和 ERα 与 FtM 人群中的易性癖有关，但这些多态性之间没有相互作用。我们的数据表明，ERβ 在人类典型的大脑分化中起关键作用。
ERβ 在男性和女性的人类性别分化中起关键作用。
