Kim Pj Wijnands1, Jun Chen2,3, Liming Liang3,4, Michael Mpj Verbiest5, Xihong Lin3, Willem A Helbing6, Adriana C Gittenberger-de Groot7, Peter J van der Spek8, André G Uitterlinden5,9, Régine Pm Steegers-Theunissen1. 1. Department of Obstetrics & Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. 2. Division of Biomedical Statistics & Informatics & Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA. 3. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. 4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. 5. Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. 6. Department of Paediatrics, Division of Paediatric Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. 7. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 8. Department of Bioinformatics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. 9. Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Abstract
AIM: Congenital heart diseases are the most common birth defects worldwide and leading cause of infant mortality. The perimembranous ventricular septal defect is most prevalent. Epigenetics may provide an underlying mechanism of the gene-environment interactions involved. MATERIALS & METHODS: We examined epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip in 84 case children and 196 control children. RESULTS: We identified differential methylation of a CpG locus (cg17001566) within the PRDM16 gene after Bonferroni correction (p = 9.17 × 10-8). This was validated by bisulfite pyrosequencing. PRDM16 functions as a repressor of TGF-β signaling controlling tissue morphogenesis crucial during cardiogenesis. At 15% false-discovery rate, we identified seven additional CpG loci. CONCLUSION: These findings provide novel insights in the pathogenesis of perimembranous ventricular septal defect, which is of interest for future prediction and prevention.
AIM: Congenital heart diseases are the most common birth defects worldwide and leading cause of infant mortality. The perimembranous ventricular septal defect is most prevalent. Epigenetics may provide an underlying mechanism of the gene-environment interactions involved. MATERIALS & METHODS: We examined epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip in 84 case children and 196 control children. RESULTS: We identified differential methylation of a CpG locus (cg17001566) within the PRDM16 gene after Bonferroni correction (p = 9.17 × 10-8). This was validated by bisulfite pyrosequencing. PRDM16 functions as a repressor of TGF-β signaling controlling tissue morphogenesis crucial during cardiogenesis. At 15% false-discovery rate, we identified seven additional CpG loci. CONCLUSION: These findings provide novel insights in the pathogenesis of perimembranous ventricular septal defect, which is of interest for future prediction and prevention.