Alterations in cardiac DNA methylation in human dilated cardiomyopathy

EMBO Molecular Medicine

Jan Haas⁴  Karen S. Frese⁴  Yoon Jung Park⁶  Andreas Keller²  Britta Vogel⁴  Anders M. Lindroth⁶  Dieter Weichenhan⁶  Jennifer Franke⁴  Simon Fischer⁴  Andrea Bauer¹  Sabine Marquart⁴  Farbod Sedaghat-Hamedani⁴  Elham Kayvanpour⁴  Doreen Köhler⁴  Nadine M. Wolf⁴  Sarah Hassel⁴  Rouven Nietsch⁴  Thomas Wieland³  Philipp Ehlermann⁴  Jobst-Hendrik Schultz⁵  Andreas Dösch⁴  Derliz Mereles⁴  Stefan Hardt⁴  Johannes Backs⁴  Jörg D. Hoheisel¹  Christoph Plass⁶  Hugo A. Katus⁴ 

[1] Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany;Department of Human Genetics, Saarland University, Germany;Medical Faculty Mannheim, Institute of Experimental and Clinical Pharmacology and Toxicology, Heidelberg University, Mannheim, Germany;Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany;Department of General Internal Medicine and Psychosomatics, University Hospital Heidelberg, Heidelberg, Germany;Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany

关键词: biomarker;    dilated cardiomyopathy;    DNA methylation;    epigenetics;    heart failure;   

DOI  :  10.1002/emmm.201201553

来源: Wiley

【 摘 要 】

Abstract

Dilated cardiomyopathies (DCM) show remarkable variability in their age of onset, phenotypic presentation, and clinical course. Hence, disease mechanisms must exist that modify the occurrence and progression of DCM, either by genetic or epigenetic factors that may interact with environmental stimuli. In the present study, we examined genome-wide cardiac DNA methylation in patients with idiopathic DCM and controls. We detected methylation differences in pathways related to heart disease, but also in genes with yet unknown function in DCM or heart failure, namely Lymphocyte antigen 75 (LY75), Tyrosine kinase-type cell surface receptor HER3 (ERBB3), Homeobox B13 (HOXB13) and Adenosine receptor A2A (ADORA2A). Mass-spectrometric analysis and bisulphite-sequencing enabled confirmation of the observed DNA methylation changes in independent cohorts. Aberrant DNA methylation in DCM patients was associated with significant changes in LY75 and ADORA2A mRNA expression, but not in ERBB3 and HOXB13. In vivo studies of orthologous ly75 and adora2a in zebrafish demonstrate a functional role of these genes in adaptive or maladaptive pathways in heart failure.

【 授权许可】

Unknown   
Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.