Thorac Cardiovasc Surg 2013; 61 - P10
DOI: 10.1055/s-0033-1354499

Determination of DNA Methylation Patterns in Cardiac Tissue from Hypoplastic Left Heart Syndrome

K Hoff 1, 2, 3, O Ammerpohl 2, J Kolarova 2, AK Arndt 4, K Pfeffer 5, O Toka 5, R Siebert 2, HH Kramer 1, 3
  • 1Clinic for Congenital Heart Defects and Pediatric Cardiology, Kiel
  • 2Institute of Human Genetics, Kiel
  • 3DZHK (German Centre for Cardiovascular Research), partner side Kiel
  • 4Brigham and Women's Hospital, Boston
  • 5Department of Pediatric Cardiology, Erlangen

Hypoplastic left heart syndrome (HLHS) is a congenital heart defect (CHD) characterized by severe underdevelopment of the left side of the heart. Displaying 8% sibling recurrence risk, several studies assume a genetic cause for HLHS.

Differential expression of genes through epigenetic factors could disturb cardiogenesis resulting in heart malformations, such as HLHS. Thus, the authors aimed here to investigate whether cardiac tissue from HLHS shows a distinct DNA methylation pattern.

In this study they included genomic DNA extracted from heart tissue, specifically interatrial septum (IAS) samples of 25 HLHS patients and 10 patients with right heart obstructive lesions as control. DNA methylation was assessed using Illumina's HumanMethylation450K BeadChips. To discover genes aberrantly methylated in HLHS, the authors compared the HLHS samples to those from the right heart obstructive lesions.

T-test revealed 119 CpG loci corresponding to 101 genes differentially methylated in HLHS (FDR < 0.05). The DNA methylation patterns of both groups, HLHS and control, displayed strong heterogeneity. The majority of CpG loci differentially methylated showed methylation differences of less than 4%, with only two loci showing differences of more than 10%. The results indicated that the DNA methylation differences in IAS between HLHS and right heart obstructive lesions differ only marginally. As this could be due to the fact that IAS might not be representative for the overall cardiac DNA methylation, the authors currently analyze DNA methylation patterns of different heart regions. (Supported through DZHK.)