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Alterations in cardiac DNA methylation in human dilated cardiomyopathy

  1. Jan Haas1,†,
  2. Karen S. Frese1,†,
  3. Yoon Jung Park2,3,†,
  4. Andreas Keller4,
  5. Britta Vogel1,
  6. Anders M. Lindroth2,
  7. Dieter Weichenhan2,
  8. Jennifer Franke1,
  9. Simon Fischer1,
  10. Andrea Bauer5,
  11. Sabine Marquart1,
  12. Farbod Sedaghat-Hamedani1,
  13. Elham Kayvanpour1,
  14. Doreen Köhler1,
  15. Nadine M. Wolf1,6,
  16. Sarah Hassel1,
  17. Rouven Nietsch1,
  18. Thomas Wieland6,8,
  19. Philipp Ehlermann1,
  20. Jobst-Hendrik Schultz7,
  21. Andreas Dösch1,
  22. Derliz Mereles1,
  23. Stefan Hardt1,
  24. Johannes Backs1,9,
  25. Jörg D. Hoheisel5,
  26. Christoph Plass2,9,
  27. Hugo A. Katus1,9,
  28. Benjamin Meder1,9,*

Article first published online: 22 JAN 2013

DOI: 10.1002/emmm.201201553

Issue

EMBO Molecular Medicine

EMBO Molecular Medicine

Volume 5, Issue 3, pages 413–429, March 2013

Total views since publication: 928

Additional Information

How to Cite

Haas, J., Frese, K. S., Park, Y. J., Keller, A., Vogel, B., Lindroth, A. M., Weichenhan, D., Franke, J., Fischer, S., Bauer, A., Marquart, S., Sedaghat-Hamedani, F., Kayvanpour, E., Köhler, D., Wolf, N. M., Hassel, S., Nietsch, R., Wieland, T., Ehlermann, P., Schultz, J.-H., Dösch, A., Mereles, D., Hardt, S., Backs, J., Hoheisel, J. D., Plass, C., Katus, H. A. and Meder, B. (2013), Alterations in cardiac DNA methylation in human dilated cardiomyopathy. EMBO Mol Med, 5: 413–429. doi: 10.1002/emmm.201201553

Author Information

  1. 1

    Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany

  2. 2

    Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany

  3. 3

    Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, South Korea

  4. 4

    Department of Human Genetics, Saarland University, Germany

  5. 5

    Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany

  6. 6

    Medical Faculty Mannheim, Institute of Experimental and Clinical Pharmacology and Toxicology, Heidelberg University, Mannheim, Germany

  7. 7

    Department of General Internal Medicine and Psychosomatics, University Hospital Heidelberg, Heidelberg, Germany

  8. 8

    DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany

  9. 9

    DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, Germany

  1. †

    These authors contributed equally to this work.

*Tel: +49 6221564835; Fax: +49 6221564645

  • †

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 5 MAR 2013
  2. Article first published online: 22 JAN 2013
  3. Manuscript Accepted: 29 NOV 2012
  4. Manuscript Revised: 15 NOV 2012
  5. Manuscript Received: 8 MAY 2012

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Keywords:

  • biomarker;
  • dilated cardiomyopathy;
  • DNA methylation;
  • epigenetics;
  • heart failure

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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