Gene regulatory networks in atrial fibrillation

Atrial fibrillation(AF)is the most frequent arrhythmogenic syndrome in humans.With an estimate incidence of1%-2%in the general population,AF raises up to almost10%-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.