Open Access

ARTICLE

DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Congenital Heart Diseases

by Shuliang Xia^1,2,3,#, Huikang Tao^2,#, Shixin Su⁴, Xinxin Chen², Li Ma², Jianru Li⁵, Bei Gao⁶, Xumei Liu⁵, Lei Pi⁷, Jinqing Feng⁴, Fengxiang Li², Jia Li^4,*, Zhiwei Zhang^1,3,*

1 Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, 510100, China
2 Department of Cardiovascular Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China
3 Department of Pediatric Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, 510100, China
4 Clinical Physiology Laboratory, Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou, 510623, China
5 Department of Echocardiogram, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China
6 Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, 63130, USA
7 Clinical Biological Resource Bank of Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510623, China

* Corresponding Authors: Jia Li. Email: ; Zhiwei Zhang. Email:

Congenital Heart Disease 2024, 19(2), 247-256. https://doi.org/10.32604/chd.2024.052583

Received 07 April 2024; Accepted 28 April 2024; Issue published 16 May 2024

Abstract

Aims: 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). Methods and Results: 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. Conclusion: 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.

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