The study of expression levels of DNA methylation regulators in patients affected with congenital heart defects (CHDs)

Abstract

Background: Congenial heart defects (CHDs) have multifactorial etiology with complex interplay of genetic and environmental factors. Environmental impact can have epigenetic mechanism of CHD development. Many studies have reported the causal association between CHD and distinct DNA methylation profile which is one of the key epigenetic events, which has vital role in normal embryonic development. The products of DNMT1, DNMT3A, DNMT3B, and MBD2 are important regulators of DNA methylation process.Changes in the expression of these genes are implicated in congenital structural cardiac defects. Hence, in this proof-of-concept study, we have compared the expression levels of these genes in the blood samples of healthy controls and CHD cases while investigating the etiology of CHD. Methods: In this study with 48 CHD cases and 47 healthy controls, total RNA was isolated from the whole blood samples using TRI reagent. Quantitative RT PCR (qRT-PCR) was used to analyze the mRNA levels of DNMT1, DNMT3A, DNMT3B, and MBD2. The expression levels have been analyzed by relative quantification. Results: We observed that DNMT3B (fold change = À2.563; p = .0018) and DNMT3A (fold change = À2.169; p = .05) were significantly downregulated in CHD patients, whereas the expression of DNMT1 and MBD2 was not significantly different between cases and controls.Conclusions: Lower expression of de novo methyltransferases, namely, DNMT3B and DNMT3A in CHD cases, may be an important contributor to the mechanism of CHD pathogenesis. Further studies with age-matched controls and analysis of global DNA methylation profile are required to investigate the proposed causal association.

The Role of Clonal Hematopoiesis of Indeterminant Potential and DNA (Cytosine-5)-Methyltransferase Dysregulation in Pulmonary Arterial Hypertension and Other Cardiovascular Diseases

“…Joshi et al found that the expression levels of DNMT3A and DNMT3B were significantly reduced in the blood of patients under the age of 21 with several forms of congenital heart disease, such as ventricular or atrial septal defects and pulmonary stenosis, suggesting that decreased DNMT3 activity and the related genome's hypomethylation may contribute to the pathogenesis of CHDs [144]. Sheng et al found that patients with tetralogy of Fallot (TOF) have significantly lower methylation levels of LINE-1 and lower global DNA methylation levels compared to healthy individuals [145].…”