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Maintenance of Low Inflammation Level by the ZFHX3 SNP Rs2106261 Minor Allele Contributes to Reduced Atrial Fibrillation Recurrence After Pulmonary Vein Isolation

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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References
1.
Canpolat U, Aytemir K, Yorgun H, Sahiner L, Kaya E, Kabakci G . Role of preablation neutrophil/lymphocyte ratio on outcomes of cryoballoon-based atrial fibrillation ablation. Am J Cardiol. 2013; 112(4):513-9. DOI: 10.1016/j.amjcard.2013.04.015. View

2.
Jiang Z, Dai L, Song Z, Li H, Shu M . Association between C-reactive protein and atrial fibrillation recurrence after catheter ablation: a meta-analysis. Clin Cardiol. 2013; 36(9):548-54. PMC: 6649439. DOI: 10.1002/clc.22157. View

3.
Makita Y, Nakano Y, Oda N, Suenari K, Sairaku A, Kajihara K . Use of preprocedural multidetector computed tomography to decrease atrial fibrillation recurrence following extensive encircling circumferential pulmonary vein isolation. J Cardiol. 2012; 60(3):236-41. DOI: 10.1016/j.jjcc.2012.03.007. View

4.
Ellinor P, Lunetta K, Albert C, Glazer N, Ritchie M, Smith A . Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet. 2012; 44(6):670-5. PMC: 3366038. DOI: 10.1038/ng.2261. View

5.
Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M . Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003; 34(4):395-402. DOI: 10.1038/ng1206. View