EMBO Molecular Medicine (Jan 2013)
Alterations in cardiac DNA methylation in human dilated cardiomyopathy
- Jan Haas,
- Karen S. Frese,
- Yoon Jung Park,
- Andreas Keller,
- Britta Vogel,
- Anders M. Lindroth,
- Dieter Weichenhan,
- Jennifer Franke,
- Simon Fischer,
- Andrea Bauer,
- Sabine Marquart,
- Farbod Sedaghat‐Hamedani,
- Elham Kayvanpour,
- Doreen Köhler,
- Nadine M. Wolf,
- Sarah Hassel,
- Rouven Nietsch,
- Thomas Wieland,
- Philipp Ehlermann,
- Jobst‐Hendrik Schultz,
- Andreas Dösch,
- Derliz Mereles,
- Stefan Hardt,
- Johannes Backs,
- Jörg D. Hoheisel,
- Christoph Plass,
- Hugo A. Katus,
- Benjamin Meder
Affiliations
- Jan Haas
- Department of Internal Medicine III, University of Heidelberg
- Karen S. Frese
- Department of Internal Medicine III, University of Heidelberg
- Yoon Jung Park
- Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ)
- Andreas Keller
- Department of Human Genetics, Saarland University
- Britta Vogel
- Department of Internal Medicine III, University of Heidelberg
- Anders M. Lindroth
- Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ)
- Dieter Weichenhan
- Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ)
- Jennifer Franke
- Department of Internal Medicine III, University of Heidelberg
- Simon Fischer
- Department of Internal Medicine III, University of Heidelberg
- Andrea Bauer
- Division of Functional Genome Analysis, German Cancer Research Center (DKFZ)
- Sabine Marquart
- Department of Internal Medicine III, University of Heidelberg
- Farbod Sedaghat‐Hamedani
- Department of Internal Medicine III, University of Heidelberg
- Elham Kayvanpour
- Department of Internal Medicine III, University of Heidelberg
- Doreen Köhler
- Department of Internal Medicine III, University of Heidelberg
- Nadine M. Wolf
- Department of Internal Medicine III, University of Heidelberg
- Sarah Hassel
- Department of Internal Medicine III, University of Heidelberg
- Rouven Nietsch
- Department of Internal Medicine III, University of Heidelberg
- Thomas Wieland
- Medical Faculty Mannheim, Institute of Experimental and Clinical Pharmacology and Toxicology, Heidelberg University
- Philipp Ehlermann
- Department of Internal Medicine III, University of Heidelberg
- Jobst‐Hendrik Schultz
- Department of General Internal Medicine and Psychosomatics, University Hospital Heidelberg
- Andreas Dösch
- Department of Internal Medicine III, University of Heidelberg
- Derliz Mereles
- Department of Internal Medicine III, University of Heidelberg
- Stefan Hardt
- Department of Internal Medicine III, University of Heidelberg
- Johannes Backs
- Department of Internal Medicine III, University of Heidelberg
- Jörg D. Hoheisel
- Division of Functional Genome Analysis, German Cancer Research Center (DKFZ)
- Christoph Plass
- Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ)
- Hugo A. Katus
- Department of Internal Medicine III, University of Heidelberg
- Benjamin Meder
- Department of Internal Medicine III, University of Heidelberg
- DOI
- https://doi.org/10.1002/emmm.201201553
- Journal volume & issue
-
Vol. 5,
no. 3
pp. 413 – 429
Abstract
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.
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