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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.

SUBMITTER: Tomomori S

PROVIDER: S-EPMC6122824 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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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.

Tomomori Shunsuke S Nakano Yukiko Y Ochi Hidenori H Onohara Yuko Y Sairaku Akinori A Tokuyama Takehito T Motoda Chikaaki C Matsumura Hiroya H Amioka Michitaka M Hironobe Naoya N Ookubo Yousaku Y Okamura Shou S Kawazoe Hiroshi H Chayama Kazuaki K Kihara Yasuki Y

PloS one 20180904 9

<h4>Introduction</h4>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.<h4>Methods</h4>We genotyped ZFHX ...[more]

PMID: 30180182

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Project description:BackgroundPulmonary vein isolation (PVI) is an effective treatment strategy for patients with atrial fibrillation (AF), but many experience AF recurrence and require repeat ablation procedures. The goal of this study was to develop and evaluate a methodology that combines machine learning (ML) and personalized computational modeling to predict, before PVI, which patients are most likely to experience AF recurrence after PVI.MethodsThis single-center retrospective proof-of-concept study included 32 patients with documented paroxysmal AF who underwent PVI and had preprocedural late gadolinium enhanced magnetic resonance imaging. For each patient, a personalized computational model of the left atrium simulated AF induction via rapid pacing. Features were derived from pre-PVI late gadolinium enhanced magnetic resonance images and from results of simulations of AF induction. The most predictive features were used as input to a quadratic discriminant analysis ML classifier, which was trained, optimized, and evaluated with 10-fold nested cross-validation to predict the probability of AF recurrence post-PVI.ResultsIn our cohort, the ML classifier predicted probability of AF recurrence with an average validation sensitivity and specificity of 82% and 89%, respectively, and a validation area under the curve of 0.82. Dissecting the relative contributions of simulations of AF induction and raw images to the predictive capability of the ML classifier, we found that when only features from simulations of AF induction were used to train the ML classifier, its performance remained similar (validation area under the curve, 0.81). However, when only features extracted from raw images were used for training, the validation area under the curve significantly decreased (0.47).ConclusionsML and personalized computational modeling can be used together to accurately predict, using only pre-PVI late gadolinium enhanced magnetic resonance imaging scans as input, whether a patient is likely to experience AF recurrence following PVI, even when the patient cohort is small.

Dataset Information

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

Publications

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

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