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

Abstract

IntroductionThe 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.MethodsWe 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.ResultsThe 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).ConclusionsThe 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.

Minor allele of GJA1 gene polymorphism is associated with higher heart rate during atrial fibrillation

“…A continuous PVI was performed in all subjects using an open-irrigation 3.5-mm tip deflectable catheter (THERMOCOOL SMARTOUCH; Biosense Webster) under the guidance of a 3-dimensional electro-anatomical mapping system (CARTO3, Biosense Webster) with computed tomography integration (CARTOMERGE, Biosense Webster) to achieve electrical isolation of the left- and right-sided pulmonary veins. We confirmed the PVI entrance and exit block and then rechecked these under the infusion of isoproterenol plus adenosine triphosphate 23 .…”

“…A continuous PVI was performed in all subjects using an open-irrigation 3.5-mm tip deflectable catheter (THERMOCOOL SMARTOUCH; Biosense Webster) under the guidance of a 3-dimensional electro-anatomical mapping system (CARTO3, Biosense Webster) with computed tomography integration (CARTOMERGE, www.nature.com/scientificreports/ Biosense Webster) to achieve electrical isolation of the left-and right-sided pulmonary veins. We confirmed the PVI entrance and exit block and then rechecked these under the infusion of isoproterenol plus adenosine triphosphate 23 . After the PVI, an EPS was performed during stable SR. Four 5-French-gauge catheters were used: one catheter was a 10-polar electrode catheter positioned in the CS, and three catheters were quadripolar electrode catheters positioned in the HRA, His bundle, and right ventricle, all with a 5-mm interelectrode distance.…”

“…The SNRT was measured as the recovery interval after a 30-s stimulation from the HRA. The CSRT was defined as the recovery interval in excess of the sinus cycle (i.e., CSRT = maximum SNRT − sinus cycle length) 23 . The ERP was measured using extrastimulus pacing with varied coupling intervals at a basic cycle length of 600 ms.…”

Association between ZFHX3 and PRR X1 polymorphisms and atrial fibrillation susceptibility

“…Taking into consideration the more precise assessment of the ZFHX3 rs2106261 and PRRX1 rs3903239 variants in AF risk, we must rst perform a meta-analysis of all eligible case-control studies to con rm the associations [18,[22][23][24][25][26][27].…”

Association Between ZFHX3 and PRRX1 Genes’ Two Common Polymorphisms and Atrial Fibrillation Susceptibility in Asians

“…Taking into consideration of a more precise assessment of ZFHX3 rs2106261 and PRRX1 rs3903239 variants in AF risk, hence, we must rst perform a metaanalysis of all eligible case-control studies to con rm [18,[22][23][24][25][26][27].…”