4q25 and ZFHX3 Single Nucleotide Polymorphisms are Associated with Electroanatomical Characteristics of Left Atrium and Clinical Outcomes of Radiofrequency Catheter Ablation in Patients with Atrial Fibrillation

Previous studies have demonstrated an association between several single nucleotide polymorphisms and atrial fibrillation (AF). We hypothesized that the phenotypes of AF patients were associated with common AF susceptibility alleles. Subjects and Methods: A total of 659 patients (579 years, 76% male) with AF who underwent catheter ablation and 659 age, and sex-matched controls were genotyped for the common AF susceptibility alleles rs2200733 and rs6843082 at 4q25, rs2106261 at ZFHX3, and rs13376333 at KCNN3. The phenotypes of AF patients, including electroanatomical characteristics of the left atrium and recurrence after ablation, were compared. Results: The rs2200733 variant allele carriers have larger left atrium volume (128.540.7 vs. 113.529.2 mL, p=0.020), longer PR interval (185.932.6 vs. 174.821.9 ms, p=0.018), and higher amplitude of negative P-wave terminal force in Lead V1 (0.070.04 vs. 0.050.04 mV, p=0.015) on electrocardiography than those without the variant allele. When the patients were assigned to three groups according to the number of variant alleles (Group A: no variant, n=15; Group B: 1 variant, n=158; Group C: 2 variants, n=439), incremental prognostic value, according to the number of variant alleles, was demonstrated (Log Rank p=0.015). Multivariate Cox regression analysis showed that persistent AF (OR 1.677, 95% CI 1.176-2.381, p=0.004) and the number of variants (OR 1.552, 95% CI 1.099-2.222, p=0.015) were independent predictors for recurrence of AF. Conclusion: This study showed the common AF susceptibility alleles at 4q25 and ZFHX3 are associated with electroanatomical characteristics of the left atrium and the clinical outcomes of catheter ablation in Korean patients with AF.