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

Background: Atrial fibrillation (AF) and recurrence of AF after pulmonary vein isolation (PVI) have been linked to sinus node dysfunction.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: The GJA1 SNP rs1015451, coding for a gap junction protein (connexin-43), may be considered a novel genetic marker for AF recurrence after PVI.