Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease.
Congenital heart disease
DNA methylation
Monozygotic twins
Umbilical cord blood
Journal
Genomics
ISSN: 1089-8646
Titre abrégé: Genomics
Pays: United States
ID NLM: 8800135
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
01
10
2022
revised:
04
01
2023
accepted:
19
01
2023
pubmed:
24
1
2023
medline:
21
3
2023
entrez:
23
1
2023
Statut:
ppublish
Résumé
Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth. Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR. 379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels. Specific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD. ChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.
Sections du résumé
BACKGROUND
Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth.
METHODS
Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR.
RESULTS
379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels.
CONCLUSIONS
Specific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD.
TRIAL REGISTRATION
ChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.
Identifiants
pubmed: 36690264
pii: S0888-7543(23)00009-5
doi: 10.1016/j.ygeno.2023.110565
pii:
doi:
Banques de données
ChiCTR
['ChiCTR-OOC-16008203']
Types de publication
Twin Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110565Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.