Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
EMBO Mol Med. 2013 Mar;5(3):413-29. doi: 10.1002/emmm.201201553. Epub 2013 Jan 22.

Alterations in cardiac DNA methylation in human dilated cardiomyopathy.

Author information

  • 1Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany.

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.

Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

PMID:
23341106
[PubMed - indexed for MEDLINE]
PMCID:
PMC3598081
Free PMC Article

Images from this publication.See all images (9)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk