Abstract 13920: Common Variant in Pitx2 Contributes to the Pathogenesis of Paroxysmal Atrial Fibrillation by Impairing Sinus Node Function and Progression of Atrial Remodeling

Abstract

Introduction: Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with atrial fibrillation (AF). The most notably PITX2 SNPs have been known to show the strong association with AF, but how these SNPs affect clinical phenotype of AF has not been clarified. Hypothesis: We assessed the hypothesis that PITX2 SNPs influence the cardiac structures and electrophysiological properties, and increase the susceptibility to AF. Methods: To investigate the association between the PITX2 SNP and paroxysmal atrial fibrillation (PAF), we genotyped PITX2 SNP (rs6817105) in 344 Japanese PAF patients hospitalized in Hiroshima University hospital and 1,507 healthy controls and compared the allele frequencies of the PITX2 SNP between the PAF patients and controls. The PITX2 SNP was significantly associated with PAF (minor allele (C) frequency: PAF 64.7% vs control 47.3%, P =3.7х10 − 16 , odds ratio (OR)=2.0). We investigated the relationships between the PITX2 C risk allele and clinical characteristics, ECG parameters, parameters of cardiac ultrasound, and electrophysiological study. Results: There were significant linear correlations between the PITX2 genotypes(CC, CT, and TT) and the max sinus node recovery time(SNRT) , corrected sinus node recovery time(CSNRT) and left atrial diameter (LAD) (max SNRT, CC: 1328ms, CT: 1235ms , TT: 1225ms , P =1.5х10 − 2 , CSNRT, CC: 482ms, CT: 418ms, TT: 409ms ,P =1.3х10 − 2 , LAD; CC:37.2±5.6mm, CT:34.4±5.3mm, TT:34.1±5mm, P=1.3х10 − 2 , respectively). Conclusions: To the best of our knowledge, this was the first report showing that PITX2 risk allele was related to the sinus node dysfunction and progression of atrial remodeling in humans. The result was meaningful for considering the mechanism of why PITX2 contributes to the pathogenesis of AF.