Thorac cardiovasc Surg 2017; 65(S 02): S111-S142
DOI: 10.1055/s-0037-1599000
DGPK Oral Presentations
Monday, February 13th, 2017
DGPK: Young Investigators Award
Georg Thieme Verlag KG Stuttgart · New York

Differential DNA-Methylation Pattern in Cardiac Tissue Samples from Patients with Congenital Heart Disease

K. Hoff1, A. Kahlert1, E. Audain1, H. Milting4, R. Siebert5, H.-H. Kramer1, O. Ammerpohl6, M.-P. Hitz1
  • 1Universitätsklinikum Schleswig-Holstein, Klinik für angeborene Herzfehler und Kinderkardiologie, Kiel, Germany
  • 2DZHK (German Centre for Cardiovascular Research), Partner Site Kiel, Kiel, Germany
  • 3Medizinische Fakultät Carl Gustav Carus, Institut für Klinische Genetik, Dresden, Germany
  • 4Herz- und Diabeteszentrum NRW, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, Bad Oeynhausen, Germany
  • 5Universität Ulm, Institut für Humangenetik, Ulm, Germany
  • 6Christian-Albrechts-Universität Kiel, Institut für Humangenetik, Kiel, Germany
  • 7Wellcome Trust Sanger Institute, Cambridge, United Kingdom
Further Information

Publication History

Publication Date:
02 February 2017 (online)

 
 

    Similar to other types of diseases, congenital heart disease (CHD) has been associated with aberrant epigenetic modifications. In particular DNA-methylation, essential during early mammalian development, plays a key role in tissue differentiation. Although it is possible to distinguish different types of cardiac cells by their protein and/or RNA expression profiles, patterns of differentially methylated DNA have not been systematically assessed among heart tissue samples to identify consistent changes in patients with CHD. Therefore, we analyzed tissue samples from different heart regions of affected individuals to further investigate the role of DNA-methylation in CHD. We investigated 68 genomic DNA samples from patients with different types of CHD, including samples from left and right atrium (LA, RA), left and right ventricle (LV, RV), as well as the interatrial septum (IAS). Furthermore, we accessed nine non-failing heart samples to recapitulate our methods and findings. The analysis was done using Illumina's Infinnium Human Methylation 450 Bead Chip Array. Following quality control and normalization, statistical analysis was performed using the Qlucore Omics Explorer 2.3 software. For downstream verification of identified differentially methylated loci, we applied mass spectrometric Epityper technique and bisulfite pyrosequencing. Principal component analysis revealed a distinct aggregation of atrial (LA, RA, IAS) and ventricular (LV, RV) samples. Overall, 168 CpGs could be shown to be significantly differentially methylated between atrium and ventricle samples (q ≤ 1 × 10–6), showing methylation differences of greater than 30%. Atrial samples displayed hypomethylation of these loci compared with ventricular samples. These results have been verified by techniques mentioned above and independently validated in the non-failing heart samples. With the current sample size and lacking access to healthy age-matched controls we were not able to find disease-specific loci. Nevertheless, the results of this study suggest that different heart regions, in particular atrium and ventricle, could be distinguished by specific DNA-methylation profiles. To test whether this observation holds true, we are currently testing additional samples in an independent cohort of adult specimens. In summary, our study shows the importance of methylation patterns in different parts of the heart and could provide novel insight for in vivo differentiation of cardiomyocytes.


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    No conflict of interest has been declared by the author(s).