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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Med Genet. Feb 27, 2016; 6(1): 1-16
Published online Feb 27, 2016. doi: 10.5496/wjmg.v6.i1.1
Gene regulatory networks in atrial fibrillation
Diego Franco, Estefanía Lozano-Velasco, Amelia Aranega
Diego Franco, Estefanía Lozano-Velasco, Amelia Aranega, Cardiovascular Development Group, Department of Experimental Biology B3-362, Faculty of Experimental Sciences, University of Jaén, 23071 Jaén, Spain
Author contributions: Franco D wrote the manuscript; Lozano-Velasco E and Aranega E critically read the manuscript.
Supported by A CNIC translational grant (CNIC2006/08) to Franco D; and the University of Jaén on translational biomedicine to Franco D (UJA2013/01).
Conflict-of-interest statement: The authors declare that they have not conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Diego Franco, Professor, Cardiovascular Development Group, Department of Experimental Biology B3-362, Faculty of Experimental Sciences, University of Jaén, CU Las Lagunillas s/n, 23071 Jaén, Spain. dfranco@ujaen.es
Telephone: +34-953-212763 Fax: +34-953-211875
Received: September 29, 2015
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
Processing time: 126 Days and 21.4 Hours
Abstract

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.

Keywords: Atrial fibrillation; Genetics; MicroRNAs; Genome-wide association studies; PITX2

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.