TY - JOUR
T1 - Alterations in cardiac DNA methylation in human dilated cardiomyopathy
AU - Haas, Jan
AU - Frese, Karen S.
AU - Park, Yoon Jung
AU - Keller, Andreas
AU - Vogel, Britta
AU - Lindroth, Anders M.
AU - Weichenhan, Dieter
AU - Franke, Jennifer
AU - Fischer, Simon
AU - Bauer, Andrea
AU - Marquart, Sabine
AU - Sedaghat-Hamedani, Farbod
AU - Kayvanpour, Elham
AU - Köhler, Doreen
AU - Wolf, Nadine M.
AU - Hassel, Sarah
AU - Nietsch, Rouven
AU - Wieland, Thomas
AU - Ehlermann, Philipp
AU - Schultz, Jobst Hendrik
AU - Dösch, Andreas
AU - Mereles, Derliz
AU - Hardt, Stefan
AU - Backs, Johannes
AU - Hoheisel, Jörg D.
AU - Plass, Christoph
AU - Katus, Hugo A.
AU - Meder, Benjamin
PY - 2013/3
Y1 - 2013/3
N2 - 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. Dilated cardiomyopathy is one the most frequent heart muscle diseases, which is responsible for one third of all heart failure cases. Here, the authors show widespread changes in DNA methylation patterns responsible for the disease.
AB - 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. Dilated cardiomyopathy is one the most frequent heart muscle diseases, which is responsible for one third of all heart failure cases. Here, the authors show widespread changes in DNA methylation patterns responsible for the disease.
KW - Biomarker
KW - DNA methylation
KW - Dilated cardiomyopathy
KW - Epigenetics
KW - Heart failure
UR - http://www.scopus.com/inward/record.url?scp=84874746425&partnerID=8YFLogxK
U2 - 10.1002/emmm.201201553
DO - 10.1002/emmm.201201553
M3 - Article
C2 - 23341106
AN - SCOPUS:84874746425
SN - 1757-4676
VL - 5
SP - 413
EP - 429
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 3
ER -