Abstract 16047: Novel Association of Polymorphic Genetic Variants With Baseline PR Interval in Patients With Atrial Fibrillation: New Directions From a Prospective Study (DECAF)
Background: Prolongation of the PR interval in the electrocardiogram (ECG) is known to be associated with increased risk of atrial fibrillation (AF). We examined the association of selected single nucleotide polymorphisms (SNPs) with PR interval in AF patients.
Methods: Four hundred AF patients undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-related SNPS from blood samples were performed using Qiagen QiaAMP kit and TaqMan assay respectively. A total of 371 DNA samples were available for genotyping. Multivariate linear regression analyses (after adjusting for age, gender, BMI, AF type) were applied to test allelic association (for minor allelic frequency) with baseline PR interval. PR interval duration in millisecond (ms) was derived from 12-lead ECGs recorded at the time of patient enrollment.
Results: Three hundred seventy-one AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were included in the analysis. Two SNPs, rs3807989 and rs7193343 were identified to have significant association with baseline PR interval.
For rs3807989 (7q31), median [interquartile range] of PR interval durations were 174 (149-202), 169 (145-194), 162 (137-184) ms for AA, AG, GG (risk allele: A) respectively. The regression analysis for rs3807989 in a dominant model, showed significant allelic association (regression coefficient (beta) 9.8 [95% CI 1.58 to 18.02], p=0.019) with prolonged PR interval.
For rs7193343, median [interquartile range] of PR interval durations were 169 (144-194), 162 (142-184), 154 (128-186) ms for CC, CT, TT (risk allele: T) respectively. When considering the effect of rs7193343 fitted with an additive model, significant inverse association with PR interval was observed (beta -7.4 [95% CI -14.23 to -2.63], p=0.032).
Conclusion: We identified two novel genetic markers located near developmental genes CAV1 and ZFHX3 to be associated with PR interval; rs3807989 correlated directly with prolonged PR duration while rs7193343 demonstrated inverse correlation with the phenotype. Defining the etiology of this differential association will provide important insight into underlying AF mechanisms.
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, AtriCure Inc., EpiEP. R. Bai: None. A. Al-Ahmad: None. R. Horton: None. J. Burkhardt: None. J. Sanchez: None. J. Zagrodzky: None. S. Bailey: None. G.J. Gallinghouse: None. P. Hranitzky: None. V.R. Iyer: None. A. Natale: Consultant/Advisory Board; Modest; biosense webster, janssen Pharmaceuticals, St. Jude Medical, Medtronic Inc, boston scientific corp..
- © 2015 by American Heart Association, Inc.