Abstract 15318: Association of Single-Nucleotide Polymorphisms with Left Atrial Scar in Patients with Atrial Fibrillation
Introduction: Earlier studies have demonstrated that some AF patients develop spontaneous atrial scarring that leads to genesis and perpetuation of the arrhythmia. However, it is still unclear why it happens in some and not in others. Therefore, we hypothesized that the atrial scar phenotype is associated with certain specific genetic variants and examined the relationship between AF-related single-nucleotide polymorphisms (SNP) and left atrial scar.
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 at our center. DNA extraction and genotyping for 16 AF-associated SNPS identified by GWAS study were performed from the collected blood samples using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. The Hardy-Weinberg equilibrium was assessed using Chi-square analyses. Multivariable logistic model was utilized to identify predictors of LA scar after adjusting for age, gender, LA size, hypertension and diabetes mellitus and odds ratio (OR) and 95% confidence intervals were computed.
Results: Of all 16 SNPs, rs3807989 showed a strong inverse association with LA scar at univariate analysis (0.54 [0.348-0.89] p= 0.014) in the overall population. After adjustment for covariates, the association became highly significant indicating a 50% reduction in scar risk (OR 0.50 (0.30-0.83) p=0.007). When stratified by type of AF, rs3807989 genotype predicted a substantially stronger 69% risk-reduction in the non-PAF population (OR 0.31 (0.15-0.62) p=0.0009).
Conclusion: The SNP, rs3807989 on chromosome 7p31, was demonstrated to be associated with reduced risk of left atrial scar formation in AF patients. This genetic variant is located in close proximity to the caveolin-1 gene which is known to have an anti-fibrotic role by inhibiting transforming growth factor-β1, a key mediator in the fibrosis process. Therefore, it can be postulated that by some unknown mechanism the candidate chromosomal variant potentially upregulates caveolin-1 function resulting in attenuation of fibrosis and scar formation.
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.