Document Detail

Beta1-adrenoceptor polymorphism predicts flecainide action in patients with atrial fibrillation.
MedLine Citation:
PMID:  20625396     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Antiarrhythmic action of flecainide is based on sodium channel blockade. Beta(1)-adrenoceptor (beta(1)AR) activation induces sodium channel inhibition, too. The aim of the present study was to evaluate the impact of different beta(1)AR genotypes on antiarrhythmic action of flecainide in patients with structural heart disease and atrial fibrillation.
METHODOLOGY/PRINCIPAL FINDINGS: In 145 subjects, 87 with atrial fibrillation, genotyping was performed to identify the individual beta(1)AR Arg389Gly and Ser49Gly polymorphism. Resting heart rate during atrial fibrillation and success of flecainide-induced cardioversion were correlated with beta(1)AR genotype. The overall cardioversion rate with flecainide was 39%. The Arg389Arg genotype was associated with the highest cardioversion rate (55.5%; OR 3.30; 95% CI; 1.34-8.13; p = 0.003) compared to patients with Arg389Gly (29.5%; OR 0.44; 95% CI; 0.18-1.06; p = 0.066) and Gly389Gly (14%; OR 0.24; 95% CI 0.03-2.07; p = 0.17) variants. The single Ser49Gly polymorphism did not influence the conversion rate. In combination, patients with Arg389Gly-Ser49Gly genotype displayed the lowest conversion rate with 20.8% (OR 0.31; 95% CI; 0.10-0.93; p = 0.03). In patients with Arg389Arg variants the heart rate during atrial fibrillation was significantly higher (110+/-2.7 bpm; p = 0.03 vs. other variants) compared to Arg389Gly (104.8+/-2.4 bpm) and Gly389Gly (96.9+/-5.8 bpm) carriers. The Arg389Gly-Ser49Gly genotype was more common in patients with atrial fibrillation compared to patients without atrial fibrillation (27.6% vs. 5.2%; HR 6.98; 95% CI; 1.99-24.46; p<0.001).
CONCLUSIONS: The beta(1)AR Arg389Arg genotype is associated with increased flecainide potency and higher heart rate during atrial fibrillation. The Arg389Gly-Ser49Gly genotype might be of predictive value for atrial fibrillation.
Amir M Nia; Evren Caglayan; Natig Gassanov; Tom Zimmermann; Orhan Aslan; Martin Hellmich; Firat Duru; Erland Erdmann; Stephan Rosenkranz; Fikret Er
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article     Date:  2010-07-02
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-13     Completed Date:  2010-10-28     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e11421     Citation Subset:  IM    
Department of Internal Medicine III, University of Cologne, Cologne, Germany.
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MeSH Terms
Anti-Arrhythmia Agents / therapeutic use
Atrial Fibrillation / drug therapy*,  genetics*
Flecainide / therapeutic use*
Heart Rate / drug effects
Polymorphism, Single Nucleotide / genetics*
Receptors, Adrenergic, beta-1 / genetics*
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Receptors, Adrenergic, beta-1; 54143-55-4/Flecainide

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