Abstract
Polycystic ovarian syndrome (PCOS) is a complex disorder affecting up to 15–20% of reproductive women. PCOS has recently been investigated using genome-wide association studies revealing important mutations and DNA methylation sites associated with the syndrome. As a clinically highly heterogenous condition, studying the molecular basis of the differential manifestation of PCOS is both meaningful concerning individualized management and important for understanding the biology of PCOS. Using genome-wide DNA methylation data collected from PCOS patients, we performed a powerful region-based analysis to detect differentially methylated regions (DMR) by correlating DNA methylation pattern in a genomic region with the level of each PCOS clinical sub-phenotype. We identified seven significant DMRs on chromosome 19 (12877188-12876846 bp) and chromosome 6 (MHC region) associated with prolactin level, as well as chromosomes 11 and 2 associated with metabolic attributes. Functional annotation linked significant DNA methylation patterns to functional genes (HOOK2, BDNFl, HLA-G, HLA-H, HLA-J, RNF39, etc) of metabolic disorders and immunity or novel associations to serve as targets for validation and replication.
摘要
多囊卵巢综合征(PCOS)是一种复杂的疾病, 影响多达15-20%的育龄期妇女。最近通过全基因组关联研究揭示了与PCOS相关的重要突变和DNA甲基化位点。作为一种临床高度异质性的疾病, 研究多囊卵巢综合征差异表现的分子学基础, 对于个体化管理具有重要意义, 而且对PCOS特征的了解意义重大。利用从PCOS患者收集的全基因组DNA甲基化数据, 评估基因组的差异甲基化区域(DMR)甲基化情况与PCOS临床亚表型的相关性。我们在19号染色体(12877188-12876846bp)、6号染色体(MHC区), 以及与代谢属性相关的11号和2号染色体上发现了7个与泌乳素水平显著相关的DMRs。功能注释将重要的DNA甲基化情况与代谢紊乱、免疫或新关联的功能基因 (HOOK2、BDNFl、HLA-G、HLA-H、HLA-J、RNF39等) 联系起来, 是验证和复制的目标。
The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.
Disclosure statement
No potential conflict of interest was reported by the authors.