Published online Feb 27, 2016. doi: 10.5496/wjmg.v6.i1.1
Peer-review started: October 21, 2015
First decision: November 27, 2015
Revised: January 14, 2016
Accepted: February 16, 2016
Article in press: February 18, 2016
Published online: February 27, 2016
Atrial fibrillation (AF) is the most frequent arrhythmogenic syndrome in humans. With an estimate incidence of 1%-2% in the general population, AF raises up to almost 10%-12% in 80+ years. Thus, AF represents nowadays a highly prevalent medical problem generating a large economic burden. At the electrophysiological level, distinct mechanisms have been elucidated. Yet, despite its prevalence, the genetic and molecular culprits of this pandemic cardiac electrophysiological abnormality have remained largely obscure. Molecular genetics of AF familiar cases have demonstrated that single nucleotide mutations in distinct genes encoding for ion channels underlie the onset of AF, albeit such alterations only explain a minor subset of patients with AF. In recent years, analyses by means of genome-wide association studies have unraveled a more complex picture of the etiology of AF, pointing out to distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Furthermore a new layer of regulatory mechanisms have emerged, i.e., post-transcriptional regulation mediated by non-coding RNA, which have been demonstrated to exert pivotal roles in cardiac electrophysiology. In this manuscript, we aim to provide a comprehensive review of the genetic regulatory networks that if impaired exert electrophysiological abnormalities that contribute to the onset, and subsequently, on self-perpetuation of AF.
Core tip: Atrial fibrillation (AF) is the most prevalent arrhythmogenic defect in the human population. Genetic factors such as mutations in distinct ion channel encoding genes have been described, yet representing less than 10% of all AF cases. Genome wide association studies have widened the genetic culprits contributing to AF. We provide herein a state-of-the art review on the genetic components underlying AF. Experimental evidences demonstrated that PITX2 plays a pivotal role regulating cellular, molecular and electrophysiological characteristics of the developing and adult heart that, if impaired, predispose to AF, leading to complex regulatory networks with transcriptional and post-transcriptional (microRNA) regulatory mechanisms.