Abstract 15313: Novel Single-Nucleotide Polymorphisms Predict Inverse Association With Non-Pulmonary Vein Triggers in Patients With Paroxysmal Atrial Fibrillation: Results From a Prospective Study (DECAF)
Introduction: Although pulmonary veins (PV) are major sites of ectopic triggers initiating paroxysmal AF (PAF), triggers arising from non-PV sites also play a critical role in origination of PAF. As the exact mechanism of origin of the non-PV triggers is not known yet, we hypothesized that some common genetic variants are associated with the occurrence of these triggers. To examine our hypothesis we evaluated the association of several AF-specific genetic variants with prevalence of non-PV triggers in PAF patients undergoing 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 16 AF-associated SNPS were performed from collected blood samples using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. Multivariate logistic regression analysis (adjusted covariates: age, gender, LA size, hypertension and diabetes) was used for assessing predictive role of individual SNP; and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers.
Results: In the paroxysmal AF population, rs17042171 independently showed significant inverse allelic association (OR 0.41 [95%CI 0.18-0.94], p=0.035) with non-PV triggers. When fitting the kernel machine model with rs17042171 and rs11047543, risk of developing non-PV triggers decreased by 63% (adjusted OR 0.37 [95% CI 0.16-0.86], p=0.021) and 64% (adjusted OR 0.36 [95% CI 0.13-0.91], p=0.044) for the SNPs respectively.
Conclusion: Our results for the first time demonstrated an inverse association between rs17042171 and rs11047543 and non-PV triggers in PAF; presence of these SNPs conferred significant protection against development of non-PV triggers. rs17042171 and rs11047543 are located in close proximity with cardiac developmental genes PITX2 and SOX5 respectively. PITX2 is known to prevent susceptibility to atrial arrhythmia. Therefore, by some unknown mechanism these SNPs potentially modulate the expression of developmental genes causing a reduction in the risk of development of non-PV ectopic foci.
Author Disclosures: S. Mohanty: None. A.W. Hall: None. P. Mohanty: None. C. Trivedi: None. L. Di Biase: Consultant/Advisory Board; Modest; Biosense Webster, Hansen Medical, St. Jude Medical. R. Bai: None. A. Al-Ahmad: None. R. Horton: None. J.D. Burkhardt: None. J. Sanchez: None. J. Zagrodzky: None. S. Bailey: None. J.G. Gallinghouse: None. P. Hranitzky: None. V.R. Iyer: None. A. Natale: Honoraria; Modest; Biosense Webster, Janssen, Boston Scientific, Medtronic, St. Jude Medical.
- © 2014 by American Heart Association, Inc.