Genetic and epigenetic regulatory networks in atrioventricular block: mechanisms and therapeutic prospects

Atrioventricular block (AVB) is a frequent arrhythmia and can arise from both genetic predisposition and epigenetic regulation. This review provides a synopsis of the latest findings concerning the interactions of genetic-epigenetic interactions with an emphasis on mechanisms that are most likely responsible for pathobiological pathways relating to the cause of AVB. For instance, hypermethylation of the SCN5A promoter or hypomethylation ofgene transcriptionally regulates the activity of the sodium channels, and their conduction likely results in conduction disorders. We also know that miR-1 and miR-133 are significantly dysregulated in arrhythmogenic remodeling. DNA methylation of ion channels in genes is most commonly cited form of epigenetic factor among all factors mentioned above, followed by histone modifications also directed to transcription factors related to conduction. We performed a structured literature search on PubMed, Scopus, and Web of Science (2000-2025) that included human and animal studies that examined genetic and epigenetic mechanism relative to AVB. Current studies indicate a multi-tier regulatory network that incorporates inherited and environmental factors but lacks longitudinal, integrated multi-omics studies that clarify the causal pathway interaction between these systems. If we can identify interaction of genetic and epigenetic factors, we can develop valuable diagnostic and therapeutic strategies targeting AVB.