Kokosar Milana, Benrick Anna, Perfilyev Alexander, Fornes Romina, Nilsson Emma, Maliqueo Manuel, Behre Carl Johan, Sazonova Antonina, Ohlsson Claes, Ling Charlotte, Stener-Victorin Elisabet

Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.| Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.| Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Malmo, Sweden.| Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.| Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Malmo, Sweden.| Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.| Endocrinology and Metabolism Laboratory, Department of Medicine, West division, University of Chile, Santiago, Chile.| The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.| Department of Obstetrics and Gynecology, Reproductive Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.| Department of Internal Medicine, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.| Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Malmo, Sweden.| Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Sci Rep. 2016 Mar 15;6:22883. doi: 10.1038/srep22883.

Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest expression difference (CYP1B1, GPT), genes linked to PCOS (RAB5B) or type 2 diabetes (PPARG, SVEP1), and methylation (DMAP1) were replicated in a separate case-control study. In total, 63,213 sites (P < 0.05) and 440 sites (Q < 0.15) were differently methylated. Thirty differentially expressed genes had corresponding changes in 33 different DNA methylation sites. Moreover, a total number of 1913 pairs of differentially expressed "gene-CpG" probes were significantly correlated after correction for multiple testing and corresponded with 349 unique genes. In conclusion, we identified a large number of genes and pathways that are affected in adipose tissue from women with PCOS. We also identified specific DNA methylation pathways that may affect mRNA expression. Together, these novel findings show that women with PCOS have multiple transcriptional and epigenetic changes in adipose tissue that are relevant for development of the disease.