Alterations in cardiac DNA methylation in human dilated cardiomyopathy. Issue 3 (22nd January 2013)

• Record Type: Journal Article
• Authors: Haas, Jan; Frese, Karen S.; Park, Yoon Jung; Keller, Andreas; Vogel, Britta; Lindroth, Anders M.; Weichenhan, Dieter; Franke, Jennifer; Fischer, Simon; Bauer, Andrea; Marquart, Sabine; Sedaghat‐Hamedani, Farbod; Kayvanpour, Elham; Köhler, Doreen; Wolf, Nadine M.; Hassel, Sarah; Nietsch, Rouven; Wieland, Thomas; Ehlermann, Philipp; Schultz, Jobst‐Hendrik; Dösch, Andreas; Mereles, Derliz; Hardt, Stefan; Backs, Johannes; Hoheisel, Jörg D.; Plass, Christoph; Katus, Hugo A.; Meder, Benjamin
• Is Part Of: EMBO molecular medicine. Volume 5:Issue 3(2013:Mar.)
• Page Start: 413
• Page End: 429
• Publication Date: 2013-01-22
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201201553
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <italic>Lymphocyte antigen 75</italic> (<italic>LY75</italic>), <italic>Tyrosine kinase‐type cell surface receptor HER3</italic> (<italic>ERBB3</italic>), <italic>Homeobox B13</italic> (<italic>HOXB13</italic>) and <italic>Adenosine receptor A2A</italic> (<italic>ADORA2A</italic>). 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 <italic>LY75</italic> and <italic>ADORA2A</italic> mRNA expression, but not in <italic>ERBB3</italic> and <italic>HOXB13</italic>. <italic>In vivo</italic> studies of orthologous <italic>ly75</italic> and <italic>adora2a</italic> in zebrafish demonstrate a functional role of these genes in adaptive or maladaptive pathways in heart failure.</p> </abstract>