DNA methylation dysregulations in valvular atrial fibrillation

Abstract

Background The epigenetic changes underlying the development of atrial fibrillation (AF) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of AF. In the present study, we evaluated the methylation status of genomic DNA from myocardial tissue in AF patients and sinus rhythm (SR) patients systematically. Hypothesis DNA methylation dysregulations will be associated with valvular AF. Methods Right atrial myocardial tissue was obtained from rheumatic valvular patients who had undergone valve replacement surgery (SR group, n = 10; AF group, n = 10). The global DNA methylation level, the promoter methylation level of the natriuretic peptide receptor‐A gene (NPRA), and its correlation with the mRNA expression level of DNA methyltransferase genes were detected. Results The global DNA methylation level was significantly higher in the AF group than in the SR group (P < 0.05). The NPRA mRNA expression was decreased and the NPRA gene was hypermethylated in the AF group (P < 0.05). Meanwhile, the NPRA mRNA expression level has a negative correlation with the mean methylation level in the promoter region of the NPRA gene. Conclusions DNA methylation dysregulations may be relevant in the pathogenesis of AF. DNA methyltransferase 3B likely plays an essential role in the DNA methylation dysregulations in AF.

Genetics and Epigenetics of Atrial Fibrillation

“…DNA methylation is a pre-transcriptional modification, which is able to change transcriptional process, by the addition of methyl groups to specific nucleotides of the DNA. This procedure causes inactive gene expression due to the fact that the methyl binding protein prevents the transcriptional factor from binding to DNA and thus it proceed to the next step [ 200 , 201 , 202 ]. It is commonly believed that hypomethylation in diseases is more frequent than hypermethylation [ 203 ].…”

“…However, in AF context, global DNA methylation levels are significantly increased in AF patients, having a positive correlation with age [ 202 ]. Furthermore, it has been demonstrated that DNA methylation plays an important role in the maintenance of cardiac fibrosis, where DNA methyltransferases 3A ( DNMT3A ) likely plays an essential role in Ras association domain family member 1A ( RASSF1A ) mediated up-regulation of ERK1/2 [ 204 , 205 ].…”

[Retracted] Multiomics Analysis of Genetics and Epigenetics Reveals Pathogenesis and Therapeutic Targets for Atrial Fibrillation

“…DNA methylation occurs at the global and specific gene promoter level. Abnormal DNA methylation can affect the transcription and expression of key regulatory genes [ 6 ]. For example, the overall DNA methylation level of the AF group was significantly higher compared to controls [ 6 ].…”

“…Abnormal DNA methylation can affect the transcription and expression of key regulatory genes [ 6 ]. For example, the overall DNA methylation level of the AF group was significantly higher compared to controls [ 6 ]. Genome mutations are composed of single-nucleotide variants (SNVs), small insertions-deletions (indels), copy number alterations, and translocations [ 4 ].…”

The Joint Analysis of Multi-Omics Data Revealed the Methylation-Expression Regulations in Atrial Fibrillation

“…DNA methylation, a pre-transcriptional modification characterized by the addition of methyl groups to specific nucleotides, regulates the stability of gene expression states and maintains genome integrity by collaborating with proteins that modify nucleosomes (Ma et al, 2014;Tao et al, 2016;Shen et al, 2017). Previous studies considered that changes in DNA methylation states contribute to the regulation of biological processes underlying AF, such as fibrosis, atrial dilatation, atrial fibroblast proliferation and differentiation from fibroblasts into myofibroblasts (Zhao et al, 2017).…”