Novel single-nucleotide polymorphisms predict the risk of recurrence in patients with atrial fibrillation undergoing catheter ablation

background: Genome-wide association studies have identified several atrial fibrillation (AF)-associated single-nucleotide polymorphisms (SNPs). This study tested the hypothesis that selected SNPs are linked with AF recurrence following catheter ablation. Methods: Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled. DNA extraction and genotyping for AF-associated SNPs, rs6843082 and rs1448817 were performed from collected blood samples using Qiagen QiaAMP kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. Multivariate logistic regression analysis (adjusted covariates: age, gender, non-paroxysmal AF, hypertension and diabetes) was used for assessing predictive role of individual SNP with AF recurrence and false discovery rate (FDR) was computed for the candidate SNPs to address multiple testing. Patients were followed up for 1 year. Recurrence was defined as any episode of AF/ Aflutter/ AT lasting >30 seconds and was acquired by event-recorder for the first 5 months followed by series of 7-day Holter recordings at 3 months interval. results: Of 371, 207 patients (55.8%) experienced recurrence after the first procedure. In the overall AF population, rs6843082 showed significant inverse association (OR 0.536 [95%CI 0.338-0.849], p=0.008) with arrhythmia recurrence whereas rs1448817 predicted increased risk of post-ablation recurrence (OR 1.761 [95%CI 1.112-2.788], p=0.016). FDR was controlled at 1.58% for both SNPs to adjust for multiple testing. Conclusion: Our study identified two novel SNPs, rs6843082 and rs1448817 on chromosome 4q25 that are associated with the risk for arrhythmia recurrence after catheter ablation for AF; while rs6843082 confers lower risk; rs1448817 predicts increased chance of recurrence. This finding provides possible evidence of differential influence of the two SNPs on the nearby functional genes in modulating ablation outcome in atrial fibrillation patients.