Abstract 12933: A Genome-Wide Association Analysis to Identify Genomic Modulators of Rate Control Therapy in Patients with Atrial Fibrillation
Introduction: Atrial fibrillation (AF) is the most common arrhythmia requiring drug therapy, yet the response in an individual is highly variable. Rate control therapy is considered as first choice in many patients, especially those at a higher risk of AF recurrence or adverse effects related to antiarrhythmic drugs. The goal of this study was to conduct a genome wide association study (GWAS) comparing AF patients who responded effectively and ineffectively to ventricular rate control therapy.
Methods: DNA was isolated and genotyped using Illumina 610 Quad, from 287 patients (95 cases and 192 controls) enrolled in the Vanderbilt AF Registry. Cases were defined as those patients whose ventricular rates were not adequately controlled with ≥3 atrio-ventricular (AV) nodal drugs necessitating AV nodal ablation and pacemaker implantation. Controls were defined as those patients in whom the ventricular rates met the AFFIRM rate control efficacy criteria with ≤ 2 AV nodal blocking agents. All patients were of European descent and logistic regression analysis was performed with an additive model.
Results: A total of 554,041 single nucleotide polymorphisms (SNPs) with minor allele frequency >0.01 and call rate of >95% were available for analysis. Genotype association with failure to respond to ≥3 AV nodal blockers was assessed after correction for age and sex. Loci with multiple SNPs at/near genome-wide significance (Figure) within 3 genes (MYO7A [chromosome 11] P=5.29x10-6, SOX5 [chromosome 12] P=5.48x10-6, LANCL2 [chromosome 7] P=2.87x10-5) were identified.
Conclusions: This study identified multiple SNPs at/near genome-wide significance and a replication cohort will be necessary to validate the findings. Identification of genomic predictors of response to rate control therapy in patients with AF will identify new genes modulating AV nodal conduction and also support new drug development for the management of patients with this morbid condition.
- © 2011 by American Heart Association, Inc.