Alterations in cardiac DNA methylation in human dilated cardiomyopathy

被引：195

作者：

Haas, Jan ^{[1
]}

Frese, Karen S. ^{[1
]}

Park, Yoon Jung ^{[2
,3
]}

Keller, Andreas ^{[4
]}

Vogel, Britta ^{[1
]}

Lindroth, Anders M. ^{[2
]}

Weichenhan, Dieter ^{[2
]}

Franke, Jennifer ^{[1
]}

Fischer, Simon ^{[1
]}

Bauer, Andrea ^{[5
]}

Marquart, Sabine ^{[1
]}

Sedaghat-Hamedani, Farbod ^{[1
]}

Kayvanpour, Elham ^{[1
]}

Koehler, Doreen ^{[1
]}

Wolf, Nadine M. ^{[1
,6
]}

Hassel, Sarah ^{[1
]}

Nietsch, Rouven ^{[1
]}

Wieland, Thomas ^{[6
,8
]}

Ehlermann, Philipp ^{[1
]}

Schultz, Jobst-Hendrik ^{[7
]}

Doesch, Andreas ^{[1
]}

Mereles, Derliz ^{[1
]}

Hardt, Stefan ^{[1
]}

Backs, Johannes ^{[1
,9
]}

Hoheisel, Joerg D. ^{[5
]}

Plass, Christoph ^{[2
,9
]}

Katus, Hugo A. ^{[1
,9
]}

Meder, Benjamin ^{[1
,9
]}

机构：

[1] Heidelberg Univ, Dept Internal Med 3, Heidelberg, Germany

[2] German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany

[3] Ewha Womans Univ, Dept Nutr Sci & Food Management, Seoul, South Korea

[4] Univ Saarland, Dept Human Genet, D-66123 Saarbrucken, Germany

[5] German Canc Res Ctr, Div Funct Genome Anal, Heidelberg, Germany

[6] Heidelberg Univ, Med Fac Mannheim, Inst Expt & Clin Pharmacol & Toxicol, Mannheim, Germany

[7] Univ Heidelberg Hosp, Dept Gen Internal Med & Psychosomat, Heidelberg, Germany

[8] DZHK German Ctr Cardiovasc Res, Mannheim, Germany

[9] DZHK German Ctr Cardiovasc Res, Heidelberg, Germany

来源：

EMBO MOLECULAR MEDICINE | 2013年 / 5卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

biomarker; dilated cardiomyopathy; DNA methylation; epigenetics; heart failure; GENE-EXPRESSION; EPIGENETIC REGULATION; FUNCTIONAL-ANALYSIS; HEART; CTCF; TRANSCRIPTION; INSULATORS; ADENOSINE; RECEPTOR; PROTEIN;

D O I：

10.1002/emmm.201201553

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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.

引用

页码：413 / 429

页数：17

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