Maintenance of low inflammation level by the ZFHX3 SNP rs2106261 minor allele contributes to reduced atrial fibrillation recurrence after pulmonary vein isolation

The single nucleotide polymorphism (SNP) rs2106261 in the transcription factor gene ZFHX3 (16q22), a major regulator of inflammation, has been reported linking to atrial fibrillation (AF) by genome-wide association studies. Inflammation is known to be a strong predictor of atrial fibrillation recurrence after ablation, so we examined the association of the ZFHX3 SNP rs2106261 to inflammation marker expression and recurrence after AF ablation. We genotyped ZFHX3 SNP rs2106261 and compared the minor (T) allele frequency between 362 paroxysmal AF (PAF) patients underwent pulmonary vein isolation (PVI) and 627 non-AF controls. We also analyzed associations between ZFHX3 SNP rs2106261 genotype and recurrence rate after pulmonary vein isolation and the inflammation markers. The minor (T) allele frequency of the ZFHX3 SNP rs2106261 was significantly higher in AF patients than non-AF controls (odds ratio 1.52, p = 2.2×10-5). Multivariable analysis revealed that the minor allele (T) decreased AF recurrence rate after pulmonary vein isolation (hazard ratio 0.53, p = 0.04). Further, neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) expression levels were lower in PAF patients with the ZFHX3 SNP rs2106261 minor allele (TT+TC) than in CC patients (N/L ratio: CC 2.22 ± 0.08, TT+TC 1.98 ± 0.06, p = 0.018; CRP: CC 0.103 ± 0.009 mg/dl, TT+TC 0.076 ±0.007 mg/dl, p = 0.016; IL-6: CC 60.3 ± 3.0 pg/ml, TT+TC 52.8 ± 2.3 pg/ml, p = 0.04). The ZFHX3 SNP rs2106261 minor allele is associated with lower AF recurrence rate after pulmonary vein isolation. Low baseline inflammation conferred by this allele may reduce AF recurrence risk.