title: Common atrial fibrillation risk alleles at 4q25 predict recurrence after catheter-based atrial fibrillation ablation.
abstract: BACKGROUND
  Common single nucleotide polymorphisms at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical atrial fibrillation (AF). Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5%-30% of AF cases.
  
  
  OBJECTIVE
  To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases.
  
  
  METHODS
  Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years; 71% men; 89% typical AF) between 2004 and 2011. The primary end point was time to recurrence of any nonsinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF).
  
  
  RESULTS
  Two-hundred atrial tachycardia, atrial flutter, or AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76; 95% confidence interval [CI] 0.6-0.95; P = .016) compared with wild type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio 0.79; 95% CI 0.62-0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio 0.61; 95% CI 0.37-1.0; P = .037).
  
  
  CONCLUSIONS
  Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of patients with predominately typical AF. Our findings suggest that the rs2200733 polymorphism may hold promise as an objectively measured patient characteristic that can be used as a clinical tool for selecting patients for AF ablation.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37323-6602, USA.
authors.forename: M
authors.initials: M
authors.lastname: Benjamin Shoemaker
authors.forename: Raafia
authors.initials: R
authors.lastname: Muhammad
authors.forename: Babar
authors.initials: B
authors.lastname: Parvez
authors.forename: Brenda W
authors.initials: BW
authors.lastname: White
authors.forename: Megan
authors.initials: M
authors.lastname: Streur
authors.forename: Yanna
authors.initials: Y
authors.lastname: Song
authors.forename: Tanya
authors.initials: T
authors.lastname: Stubblefield
authors.forename: Gayle
authors.initials: G
authors.lastname: Kucera
authors.forename: Marcia
authors.initials: M
authors.lastname: Blair
authors.forename: Jason
authors.initials: J
authors.lastname: Rytlewski
authors.forename: Sunthosh
authors.initials: S
authors.lastname: Parvathaneni
authors.forename: Rangadham
authors.initials: R
authors.lastname: Nagarakanti
authors.forename: Pablo
authors.initials: P
authors.lastname: Saavedra
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Ellis
authors.forename: S
authors.initials: S
authors.lastname: Patrick Whalen
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.forename: Dawood
authors.initials: D
authors.lastname: Darbar R
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D017115:Catheter Ablation / Q000379:methods*; D002894:Chromosomes, Human, Pair 4; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011184:Postoperative Period; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D004247:DNA