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Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

Journal article
Authors Milana Kokosar
Anna Benrick
A. Perfilyev
R. Fornes
E. Nilsson
M. Maliqueo
Carl Johan Behre
Antonina Sazonova
Claes Ohlsson
C. Ling
Elisabet Stener-Victorin
Published in Scientific Reports
Volume 6
ISSN 2045-2322
Publication year 2016
Published at Wallenberg Laboratory
Institute of Neuroscience and Physiology, Department of Physiology
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Institute of Medicine, Department of Molecular and Clinical Medicine
Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Language en
Links dx.doi.org/10.1038/srep22883
Keywords GENOME-WIDE ASSOCIATION, MESSENGER-RNA EXPRESSION, INSULIN-RESISTANT, WOMEN, HUMAN PANCREATIC-ISLETS, DNA METHYLATION, GENE-EXPRESSION, PPAR-GAMMA, SUSCEPTIBILITY LOCI, SKELETAL-MUSCLE, SYNDROME PCOS
Subject categories Medical Genetics, Endocrinology

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.

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