Genome-Wide Association Study of Atrial Fibrillation Recurrence After Radiofrequency Catheter Ablation in a Japanese Population.

Abstract

Introduction: Catheter ablation of atrial fibrillation (AF) is an established treatment; however, recurrence remains a major issue.

Methods: This study included 606 patients with AF who underwent catheter ablation in Hiroshima University Hospital, including 143 and 463 patients with and without AF recurrence within 3 years after ablation, respectively. A logistic regression analysis and genome-wide association study (GWAS) were conducted to identify the clinical and genetic factors, respectively, associated with the AF recurrence risk.

Results: A logistic regression analysis revealed persistent AF, nonpulmonary vein AF triggers, the N-terminal pro-brain natriuretic peptide level, and the left atrial volume before catheter ablation were significant factors for recurrence (false discovery rate < 0.05). Additionally, six variants (rs2106865, rs12577119, rs12574466, rs4902609, rs8027532, and rs2032303) were associated with the AF recurrence risk, based on the GWAS results' suggestive significance (p < 5 × 10^-6). An expression quantitative trait locus analysis revealed a significant association between rs2106865 and ATP-binding cassette subfamily C member 8 (ABCC8) expression in heart tissues (atrial appendage and left ventricle). A linear regression analysis demonstrated a significant association between the ABCC8 variant rs2106865 and left atrium volume before ablation. Finally, the Cox proportional hazard model showed a significant association between the ABCC8 variant and AF recurrence (p = 1.30 × 10^-5 by log-rank test; hazard ratio 1.74, 95% confidence interval 1.38-2.20).

Conclusions: Our findings, which highlight both the clinical and genetic factors associated with AF recurrence in Japanese patients, may contribute to future efforts to improve treatment strategies for AF.