GJA1 gene polymorphism is a genetic predictor of recurrence after pulmonary vein isolation in patients with paroxysmal atrial fibrillation

Abstract

Atrial fibrillation (AF) and recurrence of AF after pulmonary vein isolation (PVI) have been linked to sinus node dysfunction. The purpose of this study was to investigate the association between the heart rate-associated single nucleotide polymorphisms (SNPs) identified in genome-wide association studies and recurrence of AF after PVI. In this study, patients with paroxysmal AF who underwent initial PVI, including 522 patients for screening and 172 patients for replication, were recruited and 21 heart rate-associated SNPs identified in genome-wide association studies were genotyped. The association between these SNPs and the recurrence of AF was investigated. Throughout the follow-up period of 21 ± 12 months, 119 patients with paroxysmal AF (22.8%) exhibited AF recurrences in the screening set. The rate of AF recurrence was significantly associated with the minor allele C of the gap junction alpha-1 protein (GJA1) rs1015451 (additive model: odds ratio 2.07; P = 9.32 × 10-7), but not with other SNPs. This association was confirmed in the replication set (allelic model: odds ratio 1.81; P = 2.70 × 10-2). Multivariate analysis revealed that the recurrence of AF after AF ablation was independently related to the GJA1 SNP rs1015451 additive model, duration of AF >1 year, AF from non-pulmonary vein foci, and thicker interventricular septum. The GJA1 SNP rs1015451, coding for a gap junction protein (connexin-43), may be considered a novel genetic marker for AF recurrence after PVI.