Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease.
Genomics
; 115(2): 110565, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36690264
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
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Cardiopatias Congênitas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
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Newborn
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article