Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.
Semin Reprod Med. 2014 May;32(3):177-82. doi: 10.1055/s-0034-1371089. Epub 2014 Apr 8.
The etiology of polycystic ovary syndrome (PCOS) has been difficult to determine because its features are heterogeneous, and its origin may also be heterogeneous. Twin studies suggest that its etiology is strongly heritable and genetic approaches are rapidly uncovering new regions of the genome that appear to confer risk for PCOS. Recent genome-wide association studies in Han Chinese women with PCOS demonstrate 11 genetic loci that are associated with PCOS. The variants identified are in regions that contain genes important for gonadotropin action, genes that are associated with risk for type 2 diabetes, and other genes in which the relationship to PCOS is not yet clear. Replication studies have demonstrated that variants at several of these loci also confer risk for PCOS in women of European ethnicity. The strongest loci in Europeans contain genes for DENND1A and THADA, with additional associations in loci containing the LHCGR and FSHR, YAP1 and RAB5/SUOX. The next steps in uncovering the pathophysiology borne out by these loci and variants will include mapping to determine the causal variant and gene, phenotype studies to determine whether these regions are associated with particular features of PCOS and functional studies of the causal variant to determine the direct cause of PCOS based on the underlying genetics. The next years will be very exciting times as groups from around the world come together to further elucidate the genetic origins of PCOS.
多囊卵巢综合征 (PCOS) 的病因一直难以确定，因为其特征具有异质性，其起源也可能具有异质性。双胞胎研究表明，其病因具有很强的遗传性，遗传方法正在迅速揭示新的基因组区域，这些区域似乎与 PCOS 的风险相关。最近对汉族 PCOS 女性进行的全基因组关联研究表明，有 11 个遗传位点与 PCOS 相关。确定的变异存在于包含促性腺激素作用的基因、与 2 型糖尿病风险相关的基因以及与 PCOS 关系尚不清楚的其他基因的区域。复制研究表明，这些位点的几种变体也会导致欧洲血统女性的 PCOS 风险。欧洲人最强的基因座包含 DENND1A 和 THADA 基因，LHCGR 和 FSHR、YAP1 和 RAB5/SUOX 基因座也有额外的关联。揭示这些基因座和变体所反映的病理生理学的下一步将包括确定因果变异体和基因的映射、确定这些区域是否与 PCOS 的特定特征相关的表型研究，以及对因果变异体的功能研究，以根据潜在的遗传学确定 PCOS 的直接原因。接下来的几年将是非常令人兴奋的时期，因为来自世界各地的团体将共同努力，进一步阐明 PCOS 的遗传起源。
