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

Abstract

Background

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

Objective

The purpose of this study was to investigate the association between the heart rate (HR)-associated single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) and recurrence of AF following the PVI.

Methods

In this study, patients with paroxysmal AF (PAF) who underwent an initial PVI, including 522 patients for screening and 172 patients for replication, were recruited and 21 HR-associated SNPs identified in GWAS 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 PAF (22.8%) exhibited AF recurrences in the screening set. The rate of AF recurrence was significantly associated with minor allele C of the gap junction alpha-1 protein (GJA1) rs1015451 (additive model, odds ratio [OR], 2.07; P = 9.32 × 10⁻⁷), but not with other SNPs. This association was confirmed in the replication set (allelic model OR, 1.81; P = 2.70 × 10⁻²). Multivariate analysis revealed that the recurrence of AF following AF ablation was independently related to the GJA1 SNP rs1015451 additive model, duration of AF longer than 1 year, AF from non-PV foci, and thicker interventricular septum.

Conclusions

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