title: Severity of obstructive sleep apnea influences the effect of genotype on response to anti-arrhythmic drug therapy for atrial fibrillation.
abstract: OBJECTIVE
  To examine the impact of genotype on the relationship between obstructive sleep apnea (OSA) and anti-arrhythmic drug (AAD) efficacy in atrial fibrillation (AF).
  
  
  METHODS
  Registry based.
  
  
  METHODS
  Clinic-based.
  
  
  METHODS
  Eighty-four individuals from Vanderbilt AF registry who had polysomnography, genotyping, and serial comprehensive evaluations of AF status.
  
  
  METHODS
  None.
  
  
  RESULTS
  Response to AADs was defined as a decrease in AF burden score by ≥ 75% or the combination of sinus rhythm on follow-up EKGs, stable AAD therapy for at least 6 months, objective AF burden below an established threshold, and the absence of non-pharmacologic therapies. Participants were genotyped for common AF susceptibility alleles at chromosomes 4q25 (near PITX2), 16q22 (in ZFHX3), and 1q21 (in KCNN3), and common SNPs in the β1-adrenergic receptor (ARDB1). Wild-type status for rs10033464 at 4q25 was associated with increased success of AAD therapy in patients with no or mild OSA (odds ratio: 10.0, 95% confidence interval: 1.03 to 97.5; p < 0.05), but did not influence response to AAD therapy in those with moderate-severe OSA. A similar trend was observed for rs1801252 on ARDB1.
  
  
  CONCLUSIONS
  In this hypothesis-generating pilot study of predominantly Caucasian men, the effect on AF response to AAD therapy of rs10033464 at 4q25 varied based on OSA status. The impact of genotype on AAD efficacy may be greatest in mild OSA and attenuated in more severe disease.
authors.affiliation: Division of Cardiovascular Medicine.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Goyal
authors.affiliation: Department of Biostatistics.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Sleep Medicine/Department of Neurology.
authors.forename: Raghu
authors.initials: R
authors.lastname: Upender
authors.affiliation: Division of Cardiovascular Medicine ; Division of Clinical Pharmacology, Vanderbilt Medical Center, Nashville, TN.
authors.forename: Dawood
authors.initials: D
authors.lastname: Darbar
authors.affiliation: Division of Cardiovascular Medicine.
authors.forename: Ken
authors.initials: K
authors.lastname: Monahan
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017286:Polysomnography; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents
keywords: anti-arrhythmic drugs; atrial fibrillation; genetics; obstructive sleep apnea