Abstract 17900: A Common Single Nucleotide Polymorphism Associated With Atrial Fibrillation Modulates Symptomatic Response To Antiarrhythmic Drug Therapy
Introduction: Recent genome wide association studies have identified 3 loci, on chromosomes 4q25 (near PITX2), 16q22 (in ZFHX3), and 1q21 (in KCNN3), that associate with either typical or lone atrial fibrillation (AF). These findings indicate that variable mechanisms contribute to AF susceptibility, and suggest therefore that response to therapy may be genotype-dependent. We tested this hypothesis by determining the relationship between response to conventional antiarrhythmic drugs (AAD) and single nucleotide polymorphisms (SNPs) that predict AF: rs2200733 and rs10033464 at 4q25, rs7193343 in ZFHX3 and rs13376333 in KCNN3.
Methods: We studied 340 Caucasian patients (225 men, 115 women; age 64±12 years) prospectively enrolled in the Vanderbilt AF Registry. AAD therapy outcome was defined prospectively as successful if the patient remained on the same AAD therapy for a minimum of 6 months with ≥75% reduction in symptomatic AF burden or non-response if AF burden was unchanged, necessitating a change in drugs or therapy.
Results: Lone AF (age<65 years, no identifiable cause) was present in 82 (24%), and hypertension was the commonest underlying disease in 180 (54%) patients. AF was paroxysmal in 238 (70%) and persistent in the remaining 102 (30%) patients. Of the 340 patients, 294 (86%) were successfully rhythm-controlled. All 4 SNPs were in Hardy-Weinberg equilibrium. Multiple clinical variables (including age, gender, hypertension, lone AF) failed to significantly predict response to AADs. By contrast rs13376333 in KCNN3 was significantly associated with successful rhythm control (odds ratio [OR] 2.01, 1.21-3.33 [95% CI]; P=0.007). This association persisted after correction for multiple clinical factors (OR 1.91, [1.16-3.13]; P=0.01).
Conclusions: These results suggest that a common SNP on chromosome 1q21 associated with incident lone AF modulates response to AAD therapy and points to a potential role for stratification of therapeutic approaches by genotype.
- © 2010 by American Heart Association, Inc.