title: PITX2-dependent gene regulation in atrial fibrillation and rhythm control.
abstract: Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. There are several major mechanisms that cause AF in patients, including a genetic predisposition to develop AF. Genome-wide association studies have identified genetic variants associated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription factor PITX2. The effect of these common gene variants on cardiac PITX2 mRNA is currently under study. PITX2 protein regulates right-left differentiation of the embryonic heart, thorax and aorta. PITX2 is expressed in the adult left atrium, but much less so in other heart chambers. Pitx2 deficiency results in electrical and structural remodelling, and impaired repair of the heart in murine models, all of which may influence AF through divergent mechanisms. PITX2 levels and single nucleotide polymorphisms on chromosome 4q25 may also be a predictor of the effectiveness of anti-arrhythmic drug therapy.
authors.affiliation: Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Fahima
authors.initials: F
authors.lastname: Syeda
authors.affiliation: Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.|Department of Cardiology, UHB NHS Trust, Birmingham, UK.|Department of Cardiology, SWBT, Birmingham, UK.
authors.forename: Paulus
authors.initials: P
authors.lastname: Kirchhof
authors.affiliation: Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.|Department of Cardiology, UHB NHS Trust, Birmingham, UK.|Department of Cardiovascular Medicine, Division of Rhythmology, University Hospital Münster, Münster, Germany.
authors.forename: Larissa
authors.identifier: 0000-0002-9241-1733
authors.initials: L
authors.lastname: Fabritz
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D001281:Atrial Fibrillation / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006325:Heart Atria / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2
keywords: Pitx2; antiarrhythmic drugs; atrial fibrillation; gene regulation; mouse model; transcription factors