DNA methylation profiles of polycystic ovarian syndrome in Chinese women: A case-control study

As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes refl ecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome using Illumina’s HumanMethylation450 BeadChip array. We identifi ed a substantial number of genomic sites diff erentially methylated in the whole blood of 30 PCOS patients and 30 healthy controls (52 sites, false discovery rate<0.05 and corresponding p value<5.68e-06 ), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related infl ammatory disorders (false discovery rate<0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profi ling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways signifi cantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.