Abstract
Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population. Its prevalence exponentially increases with age and could reach up to 8% in the elderly population. The management of AF is a complex issue that is addressed by extensive ongoing basic and clinical research. AF centers around different types of disturbances, including ion channel dysfunction, Ca2+-handling abnormalities, and structural remodeling. Genome-wide association studies (GWAS) have uncovered over 100 genetic loci associated with AF. Most of these loci point to ion channels, distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Recently, the discovery of post-transcriptional regulatory mechanisms, involving non-coding RNAs (especially microRNAs), DNA methylation, and histone modification, has allowed to decipher how a normal heart develops and which modifications are involved in reshaping the processes leading to arrhythmias. This review aims to provide a current state of the field regarding the identification and functional characterization of AF-related epigenetic regulatory networks
Highlights
Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population
These findings suggest that impaired INa current might promote AF, yet electrophysiological evidence is only available for a small subset of these point mutations
Zhang and colleagues [96] recently described an RyR2-P2328S mutant mice model presenting impaired calcium homeostasis associated to an acute atrial arrhythmogenicity while Weeke et al [97] performed a whole exome study (WES) in families with early onset lone and they identified two disease segregating rare variants in calcium voltage-gated channel auxiliary subunit beta 2 (CACNB2) and CACNA2D4 with overlapping effects on the Cav1.2 current suggesting that these variants could identify an important pathway modulating AF susceptibility
Summary
Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population [1,2]. There are many types of cardiac and medical conditions that confer increased AF risk. These include arterial hypertension, cardiomyopathies, obstructive sleep apnea, or valvular dysfunction [4,5]. Genetic variants can contribute to the AF pathophysiology by altering structure and the expression and function of proteins responsible for various cellular activities [13]. Multiple diverse epigenetic processes, including the expression of non-coding RNA molecules, DNA methylation and histone modification influence the expression of genes which in turn lead to drastic changes in the cellular structure and function, influencing the organism response to diseases [16]. In the course of this review, we will discuss the cellular and molecular basis of AF as well as the contribution of epigenetics in the disease onset and development
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