Minor Allele of GJA1 Gene Polymorphism Is Associated with Higher Heart Rate During Atrial Fibrillation

Abstract

【Background】Heart rate（HR）during atrial fibrillation（AF）varies between individuals. The genetic background of individual HR variation during AF is not well understood.【Objective】We hypothesized that HR-associated single nucleotide polymorphisms（SNPs）reported in genome-wide association studies（GWAS）are related to HR during AF.【Method】Patients with persistent AF（311 for screening and 146 for replication）who underwent AF ablation were genotyped for the 21 HR-associated SNPs reported in GWAS. The patients underwent 24-hour Holter monitoring before AF ablation and electrophysiological study after AF ablation during sinus rhythm. We analyzed relationship among total HR, clinical characteristics, electrophysiological study parameters, and SNP genotypes.【Result】A significant linear correlation was found only between GJA1 SNP（rs1015451, T＞C）and total HR（TT 110,643±17,542 beats/day, TC 116,350±19,060 beats/day, CC 122,163±25,684 beats/day, P=8.5×10⁻⁴）. We confirmed this significant correlation in the replication set. The intra-atrial conduction times were shorter in AF patients with the GJA1 minor allele than in those without it. Multivariable analysis revealed that the presence of the GJA1 SNP rs1015451 additive model, female gender, lower left ventricular ejection fraction, and higher 1 : 1 atrioventricular nodal conduction were independently associated with higher HR during AF.【Conclusion】The GJA1 SNP, a coding gap junction protein（Connexin 43）, may be a new genetic marker of higher HR in patients with AF.