TY  - EJOU
AU  - Xia, Shuliang 
AU  - Tao, Huikang 
AU  - Su, Shixin 
AU  - Chen, Xinxin 
AU  - Ma, Li 
AU  - Li, Jianru 
AU  - Gao, Bei 
AU  - Liu, Xumei 
AU  - Pi, Lei 
AU  - Feng, Jinqing 
AU  - Li, Fengxiang 
AU  - Li, Jia 
AU  - Zhang, Zhiwei 

TI  - DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Congenital Heart Diseases
T2  - Structural and Congenital Heart Disease

PY  - 2024
VL  - 19
IS  - 2
SN  - 3071-1738

AB  -  <b>Aims:</b> Multiple genes and environmental factors are known to be involved in congenital heart disease (CHD), but epigenetic variation has received little attention. Monozygotic (MZ) twins with CHD provide a unique model for exploring this phenomenon. In order to investigate the potential role of Deoxyribonucleic Acid (DNA) methylation in CHD pathogenesis, the present study examined DNA methylation variation in MZ twins discordant for CHD, especially ventricular septal defect (VSD). <b>Methods and Results:</b> Using genome-wide DNA methylation profiles, we identified 4004 differentially methylated regions (DMRs) in 18 MZ twin pairs discordant for CHD, and 2826 genes were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed a list of CHD-associated pathways. To further investigate the role of DNA methylation in VSD, data from 7 pairs of MZ twins with VSD were analyzed. We identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy, cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway by KEGG analysis, and cell-cell adhesion, calcium ion transmembrane transport by GO analysis. A proportion of DMR-associated genes were involved in calcium signaling pathways. The methylation changes of calcium signaling genes might be related to VSD pathogenesis. <b>Conclusion:</b> CHD is associated with differential DNA methylation in MZ twins. CHD may be etiologically linked to DNA methylation, and methylation of calcium signaling genes may be involved in the development of VSD.
KW  - Congenital heart disease; monozygotic twins; methylation modification; epigenetics

DO  - 10.32604/chd.2024.052583