J Korean Med Sci.  2020 Dec;35(49):e411. 10.3346/jkms.2020.35.e411.

The Effects of Single Nucleotide Polymorphisms in Korean Patients with Early-onset Atrial Fibrillation after Catheter Ablation

Affiliations
  • 1Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
  • 2Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
  • 3Division of Cardiology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea
  • 4Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
  • 5Division of Cardiology, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea

Abstract

Background
This study evaluated the status of single nucleotide polymorphisms (SNPs) in Korean patients with early-onset (< 40 years old) atrial fibrillation (AF) and their effects on the outcome after catheter ablation.
Methods
A total of 89 patients (35.7 ± 3.7 years, 81 males) with drug-refractory AF (paroxysmal 64.0%) who underwent catheter ablation were included in this study. Sixteen SNPs, including rs13376333, rs10465885, rs10033464, rs2200733, rs17042171, rs6843082, rs7193343, rs2106261, rs17570669, rs853445, rs11708996, rs6800541, rs251253, rs3807989, rs11047543, and rs3825214, were genotyped. Serial 48-hour Holter monitoring was conducted to detect AF recurrences during long-term follow up.
Results
Wild-type genotypes of rs11047543 (GG; 26/69 [37.7%] vs. GA; 13/18 [72.2%] vs. AA; 0/0 [0%], P = 0.009) and rs7193343 (CC; 0/7 [0%] vs. CT; 22/40 [55.0%] vs. TT; 18/41 [43.9%], P = 0.025) and the homozygous variant of rs3825214 (AA; 16/31 [51.6%] vs. AG; 22/43 [51.2%] vs. GG; 2/13 [15.4%], P = 0.056) were significantly associated with a lower rate of late recurrence. When the patients were assigned to four groups according to the number of risk alleles (n = 0–3), there were significant differences in recurrence rate (n = 0; 0/3 vs. n = 1; 2/13 [15.4%] vs. n = 2; 24/52 [46.2%] vs. n = 3; 13/17 [76.5%], P = 0.003). When correcting for multiple variables, rs11047543 (hazard ratio [HR], 2.723; 95% confidence interval [CI], 1.358–5.461; P = 0.005) and the number of risk alleles (HR, 2.901; 95% CI, 1.612–5.219; P < 0.001) were significantly associated with recurrence of AF after catheter ablation.
Conclusion
Polymorphisms on rs7193343 closest to ZFHX3 (16q22), rs3825214 near to TBX5 (12q24), and rs11047543 near to SOX5 (12p12) modulate the risk for AF recurrence after catheter ablation. The number of risk alleles of these 3 SNPs was an independent predictor of recurrence during long-term follow up in Korean patients with early-onset AF.

Keyword

Single Nucleotide Polymorphisms (SNPs); Atrial Fibrillation (AF); Catheter Ablation; Recurrence

Figure

  • Fig. 1 Kaplan-Meier curve of overall AF-free survival after the final ablation procedure.AF = atrial fibrillation.

  • Fig. 2 AF recurrence rates for three SNPs associated with AF. Wild-type rs11047543 (GG; 26/69 [37.7%] vs. GA; 13/18 [72.2%] vs. AA; 0/0, P = 0.009), rs7193343 (CC; 0/7 [0%] vs. CT; 22/40 [55.0%] vs. TT; 18/41 [43.9%], P = 0.025) and the homozygous variant of rs3825214 (AA; 16/31 [51.6%] vs. AG; 22/43 [51.2%] vs. GG; 2/13 [15.4%], P = 0.05) were significantly associated with a lower rate of late AF recurrence.SNP = single nucleotide polymorphism, AF = atrial fibrillation.

  • Fig. 3 Kaplan-Meier survival analysis showed incremental prognostic value according to the number of risk alleles.


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