A Comprehensive Genome-wide DNA Methylation Analysis in Blood Reveals Differentially Methylated Regions Associated with Immune Response and Steroidogenesis Pathways in Women with Polycystic Ovary Syndrome: A cross sectional study.
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引用次数: 0
Abstract
Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with a multifactorial aetiology, including genetic and epigenetic components. Despite increasing evidence highlighting the role of epigenetic modifications in PCOS, their contribution to disease progression remains unclear.
Aim: This study aimed to investigate the role of DNA methylation in the aetiology of PCOS.
Settings and design: This is a hospital-based observational study.
Materials and methods: The materials and methods of this study were to examine the role of DNA methylation in PCOS. Genomic DNA was isolated using the QIAamp DNA Mini Kit, and DNA methylation profiling was performed using the Infinium Human Methylation 850K (EPIC) array in 43 PCOS cases compared with controls.
Statistical analysis used: The Student's t-test (two-tailed) was used to compare the means and derive statistical significance from the independent groups. The ChAMP software package was used for methylation analysis on the R interface v4.2.0.
Results: Differential methylation analysis identified 243 differentially methylated CpG sites within 26 differentially methylated regions (DMRs) (|Δβ| > 0.1, P < 0.05). Notably, most DMRs were located in promoter regions near CpG islands and shores, with a significant proportion (23.07%) mapping to chromosome 6. The majority (76.9%) of DMRs exhibited hypomethylation, whereas the top two DMRs were hypermethylated. Functional enrichment analysis revealed that differentially methylated genes were associated with key pathways, including Th17 cell differentiation, steroid biosynthesis and autoimmune thyroid disease. Gene ontology analysis highlighted enrichment in immune-related biological processes, MHC protein complexes and molecular functions, including prenyltransferase and transaminase activities.
Conclusion: Our findings underscore the potential contribution of epigenetic modifications to PCOS pathogenesis, particularly through immune regulation and steroid metabolism. Further studies with larger cohorts and functional validation are warranted to establish the role of these epigenetic changes in PCOS.
背景：多囊卵巢综合征（PCOS）是一种多因素的复杂内分泌疾病，包括遗传和表观遗传因素。尽管越来越多的证据强调表观遗传修饰在多囊卵巢综合征中的作用，但它们对疾病进展的贡献仍不清楚。目的：探讨DNA甲基化在PCOS发病机制中的作用。背景和设计：这是一项以医院为基础的观察性研究。材料和方法：本研究的材料和方法是探讨DNA甲基化在PCOS中的作用。使用QIAamp DNA Mini Kit分离基因组DNA，并使用Infinium Human methylation 850K （EPIC）阵列对43例PCOS患者进行DNA甲基化分析。使用的统计分析：使用学生t检验（双尾）来比较平均值，并从独立组中获得统计显著性。在R接口v4.2.0上使用ChAMP软件包进行甲基化分析。结果：差异甲基化分析在26个差异甲基化区（DMRs）中鉴定出243个差异甲基化的CpG位点（|Δβ| > 0.1, P < 0.05）。值得注意的是，大多数DMRs位于CpG岛屿和海岸附近的启动子区域，其中较大比例（23.07%）定位于6号染色体。大多数（76.9%）DMRs表现为低甲基化，而前两个DMRs表现为高甲基化。功能富集分析显示，差异甲基化基因与关键途径相关，包括Th17细胞分化、类固醇生物合成和自身免疫性甲状腺疾病。基因本体分析强调了免疫相关生物过程、MHC蛋白复合物和分子功能的富集，包括戊烯基转移酶和转氨酶活性。结论：我们的研究结果强调了表观遗传修饰对多囊卵巢综合征发病机制的潜在贡献，特别是通过免疫调节和类固醇代谢。进一步的研究需要更大的队列和功能验证来确定这些表观遗传变化在多囊卵巢综合征中的作用。
期刊介绍：
The Journal of Human Reproductive Sciences (JHRS) (ISSN:0974-1208) a Quarterly peer-reviewed international journal is being launched in January 2008 under the auspices of Indian Society of Assisted Reproduction. The journal will cover all aspects human reproduction including Andrology, Assisted conception, Endocrinology, Physiology and Pathology, Implantation, Preimplantation Diagnosis, Preimplantation Genetic Diagnosis, Embryology as well as Ethical, Legal and Social issues. The journal will publish peer-reviewed original research papers, case reports, systematic reviews, meta-analysis, and debates.
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