NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou, China.
Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, Guangdong, 510630, China.
BMC Pregnancy Childbirth. 2024 Jan 2;24(1):5. doi: 10.1186/s12884-023-06210-3.
Polycystic ovarian syndrome (PCOS) is a common endocrine and metabolic disease in women. Hyperandrogenaemia (HA) and insulin resistance (IR) are the basic pathophysiological characteristics of PCOS. The aetiology of PCOS has not been fully identified and is generally believed to be related to the combined effects of genetic, metabolic, internal, and external factors. Current studies have not screened for PCOS susceptibility genes in a large population. Here, we aimed to study the effect of TGF-β1 methylation on the clinical PCOS phenotype.
In this study, three generations of family members with PCOS with IR as the main characteristic were selected as research subjects. Through whole exome sequencing and bioinformatic analysis, TGF-β1 was screened as the PCOS susceptibility gene in this family. The epigenetic DNA methylation level of TGF-β1 in peripheral blood was detected by heavy sulfite sequencing in patients with PCOS clinically characterised by IR, and the correlation between the DNA methylation level of the TGF-β1 gene and IR was analysed. We explored whether the degree of methylation of this gene affects IR and whether it participates in the occurrence and development of PCOS.
The results of this study suggest that the hypomethylation of the CpG4 and CpG7 sites in the TGF-β1 gene promoter may be involved in the pathogenesis of PCOS IR by affecting the expression of the TGF-β1 gene.
This study provides new insights into the aetiology and pathogenesis of PCOS.
多囊卵巢综合征（PCOS）是一种常见的女性内分泌和代谢疾病。高雄激素血症（HA）和胰岛素抵抗（IR）是 PCOS 的基本病理生理特征。PCOS 的病因尚未完全确定，一般认为与遗传、代谢、内外因素的综合作用有关。目前的研究尚未在大人群中筛选 PCOS 易感基因。本研究旨在探讨 TGF-β1 甲基化对临床 PCOS 表型的影响。
本研究选择以 IR 为主要特征的三代 PCOS 伴有 IR 的家系成员作为研究对象。通过全外显子测序和生物信息学分析，筛选出该家系中的 PCOS 易感基因 TGF-β1。采用重亚硫酸盐测序检测临床表型为 IR 的 PCOS 患者外周血 TGF-β1 基因的表观遗传 DNA 甲基化水平，并分析 TGF-β1 基因 DNA 甲基化水平与 IR 的相关性。探讨该基因的甲基化程度是否影响 IR，是否参与 PCOS 的发生发展。
本研究结果提示，TGF-β1 基因启动子 CpG4 和 CpG7 位点的低甲基化可能通过影响 TGF-β1 基因的表达而参与 PCOS IR 的发病机制。
本研究为 PCOS 的病因和发病机制提供了新的见解。
