The role of DNA methylation in syndromic and non-syndromic congenital heart disease

Abstract

Congenital heart disease (CHD) is a common structural birth defect worldwide, and defects typically occur in the walls and valves of the heart or enlarged blood vessels. Chromosomal abnormalities and genetic mutations only account for a small portion of the pathogenic mechanisms of CHD, and the etiology of most cases remains unknown. The role of epigenetics in various diseases, including CHD, has attracted increased attention. The contributions of DNA methylation, one of the most important epigenetic modifications, to CHD have not been illuminated. Increasing evidence suggests that aberrant DNA methylation is related to CHD. Here, we briefly introduce DNA methylation and CHD and then review the DNA methylation profiles during cardiac development and in CHD, abnormalities in maternal genome-wide DNA methylation patterns are also described. Whole genome methylation profile and important differentially methylated genes identified in recent years are summarized and clustered according to the sample type and methodologies. Finally, we discuss the novel technology for and prospects of CHD-related DNA methylation.

Epidemiology, Genetics and Epigenetics of Congenital Heart Diseases in Twins

“…Understanding the factors that cause molecular plasticity is difficult but it will add to our present understanding of CHD [56]. In many investigations of the heart's differential methylation profile, the tissue level is used rather than the cell level [57]. However, this is not ideal as analysis at tissue level may overlook numerous differentially methylated genes [57].…”

“…In many investigations of the heart's differential methylation profile, the tissue level is used rather than the cell level [57]. However, this is not ideal as analysis at tissue level may overlook numerous differentially methylated genes [57]. This problem is fixed by the single-cell DNA methylation sequencing technique, which helps identify stage-specific issues in signals and regulatory pathways of cardiogenesis [56,57].…”

“…However, this is not ideal as analysis at tissue level may overlook numerous differentially methylated genes [57]. This problem is fixed by the single-cell DNA methylation sequencing technique, which helps identify stage-specific issues in signals and regulatory pathways of cardiogenesis [56,57]. Because of the lack of access to human cardiac tissue during the early stages of cardiogenesis, bulk sequencing investigations (e.g., transcriptomics) have been performed on cardiac tissues obtained from terminated fetuses or surgical samples [56].…”

“…Based on this evidence, we have come to learn that MiRNAs and DNA methylation are viable indicators for the diagnosis of CHD patients before and after birth [55]. Differential DNA methylation discovered in the placenta and blood of neonate and mother is employed as a diagnostic biomarker [57]. It is now evident that demethylation therapy during pregnancy may help to minimize the risk of CHD.…”

“…It is now evident that demethylation therapy during pregnancy may help to minimize the risk of CHD. Present DNA demethylation medications work by reducing the total methylation level rather than on methylation of specific genes or regions [57].…”