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Symptomatic Response to Antiarrhythmic Drug Therapy Is Modulated by a Common Single Nucleotide Polymorphism in Atrial Fibrillation
Study Questions:
Is the response of patients with atrial fibrillation (AF) to antiarrhythmic drug therapy (AADT) genotype-dependent?
Methods:
The subjects of this study were 678 patients (mean age 63 years) with AF who received AADT. A cohort of 478 patients was assigned to a discovery group, and the remaining 198 patients were assigned to a validation group. DNA was isolated from whole blood and genotyping was performed to identify several single nucleotide polymorphisms (SNPs) known to be associated with AF. Successful AADT was defined as ≥6 months of treatment resulting in a ≥75% reduction in AF burden.
Results:
AADT was successful in 84% of patients in the discovery cohort. In the discovery cohort, a SNP (rs10033464) in the 4q25 chromosome was associated with successful AADT (odds ratio [OR], 4.7 for wild type and 3.4 for variant allele), independent of multiple clinical variables such as age, hypertension, and absence of structural heart disease. Successful AADT was achieved in 72% of patients in the validation cohort, and polymorphism at rs10033464 in this cohort was predictive of successful AADT (OR, 1.5).
Conclusions:
The authors concluded that response to AADT in patients with AF is genotype-dependent and affected by a SNP on chromosome 4q25.
Perspective:
Approximately 20% of patients with AF have the SNP identified in this study to be a predictor of the response to AADT. The results of this intriguing study suggest that therapy for AF possibly could be individualized based on genotype. For example, catheter ablation might be recommended as first-line therapy if a patient’s genotype predicts a poor response to drug therapy.
Keywords: Polymorphism, Genetic, Genotype
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