Molecular Genetics of Gender Identity Disorder

点击翻译按钮获取中文摘要

To investigate the biological mechanism of gender identity disorders (GID), I analyzed candidate genes of sex hormone, androgen receptor (AR), aromatase (CYP19), estrogene receptor (ER α and ER β), progesterone receptor gene. Subjects were 168 FTM patients (average age 28.3+/-7.6), 74 MTF patients (average age 39.4+/-10.0). Healthy controls were 276 people, 169 women (28.1 +/- 6.9 years old), 106 men (35.7 +/- 10.7 years old). The (TTTA)n repeat of the CYP19 gene, (TA)n repeat of the ER α gene, (CA)n repeat of the ER β gene, (CAG)n repeat of the AR gene, five single nucleotide polymorphism (SNP) (rs2008112 (+311G/A), V660L, H770H, rs572698, PROGINS (Alu insertion)) of the progesterone receptor gene were analyzed. I found that all the sex hormone-related genes examined did not associated with GID.Then, other candidate genes, e,g, Xist, Uspqy, Rps4y, DDx3y genes were selected based on animal studies that revealed expression in the fetal brain of these genes showed great difference between male and female, which may implied involvement in sexual identity and behaviors. Human orthologs of these genes were searched using NCBI database and those SNPs. All SNPs of Uspqy, Rps4y, DDx3y genes and 5 SNPs of the Xiest gene with known allele frequency registered in NCBI SNP database were analyzed. We found any SNP of Uspqy, Rps4y and DDx3y gene was monomorphism in Japanese population. Similarly, 3 SNPs of the Xiest gene (C43G, rs1009948, rs1794213, rs11554116) were also monomorphic. Remaining 2 SNPs of the Xiest gene, rs1894271 and rs1620574, were analyzed There was no significant diffrence of allelic and genotypic distribution between FTM patients and women, and between MTF and men. These findings may suggest that the other unknown genes may be involved in development of GIF. Therefore, genome-wide association study or gene-chip analysis of cDNA should be needed for identification of molecules of GID and further understanding of neural mechanisms of GID.