Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success

J Am Heart Assoc. 2015 Aug 13;4(8):e002046. doi: 10.1161/JAHA.115.002046.

Abstract

Background: Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF.

Methods and results: We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10(-16); PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10(-11); ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10(-14); KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation.

Conclusions: SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation.

Trial registration: ClinicalTrials.gov NCT02138695.

Keywords: atrial fibrillation; catheter ablation; genetic polymorphism; phenotype; recurrence.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asians / genetics
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / ethnology
  • Atrial Fibrillation / genetics
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / surgery*
  • Case-Control Studies
  • Catheter Ablation* / adverse effects
  • Chi-Square Distribution
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heart Conduction System / physiopathology
  • Heart Conduction System / surgery*
  • Homeodomain Proteins / genetics*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Recurrence
  • Republic of Korea
  • Risk Assessment
  • Risk Factors
  • Small-Conductance Calcium-Activated Potassium Channels / genetics
  • Time Factors
  • Transcription Factors / genetics*
  • Treatment Outcome

Substances

  • Homeodomain Proteins
  • KCNN3 protein, human
  • Small-Conductance Calcium-Activated Potassium Channels
  • Transcription Factors
  • ZFHX3 protein, human
  • homeobox protein PITX2

Associated data

  • ClinicalTrials.gov/NCT02138695