Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
PLoS One. 2013 May 21;8(5):e64801. doi: 10.1371/journal.pone.0064801. Print 2013.
Polycystic ovary syndrome (PCOS) is a complex, heterogeneous disorder of uncertain etiology. Recent studies suggested that insulin resistance (IR) plays an important role in the development of PCOS. In the current study, we aimed to investigate the molecular mechanism of IR in PCOS. We employed genome-wide methylated DNA immunoprecipitation (MeDIP) analysis to characterize genes that are differentially methylated in PCOS patients vs. healthy controls. Besides, we also identified the differentially methylated genes between patients with PCOS-non-insulin resistance (PCOS-NIR) and PCOS-insulin resistance (PCOS-IR). A total of 79 genes were differentially methylated between PCOS-NIR vs. PCOS-IR patients, and 40 genes were differentially methylated in PCOS patients vs. healthy controls. We analyzed these differentially methylated genes by constructing regulatory networks and protein-protein interaction (PPI) networks. Further, Gene Ontology (GO) and pathway enrichment analysis were also performed to investigate the biological functions of networks. We identified multiple categories of genes that were differentially methylated between PCOS-NIR and PCOS-IR patients, or between PCOS patients and healthy controls. Significantly, GO categories of immune response were differentially methylated in PCOS-IR vs. PCOS-NIR. Further, genes in cancer pathways were also differentially methylated in PCOS-NIR vs. PCOS-IR patients or in PCOS patients vs. healthy controls. The results of this current study will help to further understand the mechanism of PCOS.
多囊卵巢综合征（PCOS）是一种病因不明的复杂、异质性疾病。最近的研究表明，胰岛素抵抗（IR）在 PCOS 的发生发展中起着重要作用。在本研究中，我们旨在探讨 IR 在 PCOS 中的分子机制。我们采用全基因组甲基化 DNA 免疫沉淀（MeDIP）分析来描述 PCOS 患者与健康对照者之间差异甲基化的基因。此外，我们还鉴定了 PCOS-非胰岛素抵抗（PCOS-NIR）和 PCOS-胰岛素抵抗（PCOS-IR）患者之间差异甲基化的基因。在 PCOS-NIR 与 PCOS-IR 患者之间有 79 个基因差异甲基化，在 PCOS 患者与健康对照者之间有 40 个基因差异甲基化。我们通过构建调控网络和蛋白质-蛋白质相互作用（PPI）网络来分析这些差异甲基化基因。此外，还进行了基因本体（GO）和通路富集分析，以研究网络的生物学功能。我们鉴定了多个类别在 PCOS-NIR 与 PCOS-IR 患者之间，或在 PCOS 患者与健康对照者之间差异甲基化的基因。值得注意的是，在 PCOS-IR 与 PCOS-NIR 患者之间，免疫反应的 GO 类别差异甲基化。此外，癌症途径中的基因在 PCOS-NIR 与 PCOS-IR 患者之间或在 PCOS 患者与健康对照者之间也存在差异甲基化。本研究的结果将有助于进一步了解 PCOS 的发病机制。
