ZNF536基因调控视黄酸介导的性取向多态性的机制研究

The biological mechanism underlying homosexuality is complex, and associated with genetic factor. We have performed a genome-wide association study of male homosexuality, which demonstrating a significant association between the intron SNPrs7259428 of gene ZNF536 on the chromosomal loci 19q12 and sexual preference of male homosexuality. Gene ZNF536 is abundantly expressed in the human hypothalamus and suppresses neural differentiation induced by retinoic acid. The study aims to explore the mechanism underlying ZNF536 gene regulation of retinoic acid mediated 5-HT function, and to verify the association between ZNF 536 and homosexuality. The study will employ immunohistochemistry to compare the expression of gene ZNF536 and 5-HT1A receptor in the postmortem hypothalamic supraoptic nucleus between male homosexuality and male heterosexuality. Besides, four groups of male mice models are designed to characterize the difference of sexual preference, including mice with ZNF536 gene knock-out, mice with ZNF536 gene knock-out and fed with retinoic acid after birth, wild-type mice, and wild-type mice fed with retinoic acid after birth, and the expression of gene ZNF536 and 5-HT1A receptor in the hypothalamus is also investigated. The object of the study is to preliminarily elucidate the influence of gene ZNF536 on the 5-HT1A receptor in the hypothalamic supraoptic nucleus, as well as the sexual preference of male mice, which is of scientific significance to reveal the biological key-point of male homosexuality.

同性恋的发生机制十分复杂，其与遗传因素具有相关性。我们前期的全基因组关联分析发现：位于19q12的ZNF536基因内含子SNPrs7259428与男性同性恋性取向显著相关，分析显示该基因在人类下丘脑丰富表达，并抑制视黄酸介导的神经分化。本项目将针对ZNF536基因调控视黄酸介导的5-HT水平的的机制，明确ZNF536基因与同性恋的关联性。采用免疫组化技术分析比较男性同性恋与男性异性恋死亡后大脑下丘脑视上核的ZNF536和5-HT1A受体的表达。同时，针对ZNF536基因敲除小鼠、ZNF536基因敲除小鼠联合出生后摄入视黄酸、野生型小鼠、野生型小鼠联合出生后摄入视黄酸，比较各组动物的性取向行为差异，并检测下丘脑视上核ZNF536和5-HT1A受体表达。本项目将初步阐明ZNF536对视上核5-HT1A受体的影响及对雄性小鼠性取向形成的作用。这对揭示男性同性恋发生的关键位点具有重要的科学意义。

同性恋的发生机制十分复杂，其与遗传因素具有相关性。我们前期的全基因组关联分析发现：位于19q12的ZNF536基因内含子SNPrs7259428与男性同性恋性取向显著相关，分析显示该基因在人类下丘脑丰富表达，并抑制视黄酸介导的神经分化。本项目针对ZNF536基因调控视黄酸介导的5-HT水平的的机制，明确ZNF536基因与同性恋的关联性。采用免疫组化技术分析比较男性同性恋与男性异性恋死亡后大脑下丘脑视上核的ZNF536表达。同时，针对ZNF536基因敲除小鼠、ZNF536基因敲除小鼠联合出生后摄入视黄酸、野生型小鼠、野生型小鼠联合出生后摄入视黄酸，比较各组动物的性取向行为差异。. 结果表明，ZNF536在同性恋下丘脑视交叉上核的平均浓度显著低于异性恋男性，研究结果还发现，男性同性恋者的下丘脑视交叉上核的正中面积显著大于异性恋男性；各组小鼠性取向行为无显著的统计学差异。. 本项目将初步阐明ZNF536对视上核5-HT1A受体的影响及对雄性小鼠性取向形成的作用。这对揭示男性同性恋发生的关键位点具有重要的科学意义。