title: Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome.
abstract: 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.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Milana
authors.initials: M
authors.lastname: Kokosar
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Benrick
authors.affiliation: Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Malmö, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Perfilyev
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Romina
authors.initials: R
authors.lastname: Fornes
authors.affiliation: Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Malmö, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Nilsson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.|Endocrinology and Metabolism Laboratory, Department of Medicine, West division, University of Chile, Santiago, Chile.
authors.forename: Manuel
authors.initials: M
authors.lastname: Maliqueo
authors.affiliation: The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carl Johan
authors.initials: CJ
authors.lastname: Behre
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Antonina
authors.initials: A
authors.lastname: Sazonova
authors.affiliation: Department of Internal Medicine, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Malmö, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Stener-Victorin
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D015151:Immunoblotting; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D055815:Young Adult