Impact of a 4q25 genetic variant in atrial flutter and on the risk of atrial fibrillation after cavotricuspid isthmus ablation.
BACKGROUND
The prediction of atrial fibrillation (AF) following catheter ablation of atrial flutter (Afl) would be helpful to facilitate targeted arrhythmia monitoring and anti-coagulation strategies. A single nucleotide polymorphism, rs2200733, is strongly associated with AF. We sought to characterize the association between rs2200733 and prevalent Afl and to determine if the variant could predict AF after cavotricuspid isthmus ablation.


RESULTS
We performed a genetic association study of 295 patients with Afl and/or AF and 469 controls using multivariable logistic regression. The variant was then assessed as a predictor of incident AF after cavotricuspid isthmus ablation in 87 consecutive typical Afl patients with Cox proportional hazards models. The rs2200733 rare allele was associated with an adjusted 2.06-fold increased odds of isolated Afl (95% CI: 1.13-3.76, P = 0.019) and an adjusted 2.79-fold increased odds of a combined phenotype of AF and Afl (95% CI: 1.81-4.28, P < 0.001). Following catheter ablation for Afl, carrier status of rs2200733 failed to predict an increased risk of AF either among all subjects (adjusted HR: 0.94; 95% CI: 0.58-1.53, P = 0.806) or among those with isolated Afl (adjusted HR: 1.29; 95% CI: 0.51-3.26, P = 0.585).


CONCLUSIONS
Our study demonstrates that Afl, whether occurring in isolation or along with AF, is associated with the rs2200733 AF risk allele. Genetic carrier status of rs2200733 failed to predict an increased risk of incident or recurrent AF following catheter ablation for Afl. These findings suggest that the causal mechanism associated with rs2200733 is germane to both AF and Afl.
Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Jason D
JD
Roberts
Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Diego, San Diego, California, USA.
Jonathan C
JC
Hsu
Department of Physiological Nursing, University of California San Francisco, San Francisco, California, USA.|Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA.
Bradley E
BE
Aouizerat
Department of Physiological Nursing, University of California San Francisco, San Francisco, California, USA.|Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
Clive R
CR
Pullinger
Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.|Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Mary J
MJ
Malloy
Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.|Department of Medicine, University of California San Francisco, San Francisco, California, USA.|Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, USA.
John P
JP
Kane
Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.|Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
Jeffrey E
JE
Olgin
Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Gregory M
GM
Marcus
D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D001282:Atrial Flutter / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D017115:Catheter Ablation / Q000009:adverse effects*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D016896:Treatment Outcome; D014261:Tricuspid Valve / Q000601:surgery
atrial fibrillation; atrial flutter; catheter ablation; genetics; molecular biology