Association of atrial fibrillation susceptibility genes, atrial fibrillation phenotypes and response to catheter ablation: a gene-based analysis of GWAS data

Abstract

BackgroundPrevious studies have suggested PITX2, KCNN3 and ZFHX3 as atrial fibrillation (AF) susceptibility genes. Single common genetic polymorphisms of those genes have been linked with AF phenotypes and rhythm outcome of AF catheter ablation although their mechanisms remain elusive. New gene-based association tests may help clarifying genotype–phenotype correlations. Therefore, we hypothesized that PITX2, KCNN3 and ZFHX3 associate with left atrial enlargement and persistent AF and subsequently with ablation outcome.Methods and resultsSamples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) undergoing AF catheter ablation were genotyped for ~1,000,000 SNPs. Gene-based association was investigated using two different gene-based association tests (VEGAS, minSNP). Among the three candidate genes, only ZFHX3 associated with left atrial dilatation and AF recurrence after catheter ablation.ConclusionThis study suggests a contribution of ZFHX3 to AF remodeling and response to therapy. Future and larger studies are necessary to replicate and apply these findings with an emphasis on designing AF pathophysiology-based multi-locus risk scores.

PR Interval Associated Genes, Atrial Remodeling and Rhythm Outcome of Catheter Ablation of Atrial Fibrillation—A Gene-Based Analysis of GWAS Data

“…There are several limitations that are comparable to our previous study (Husser et al, 2017 ). This study included small sample size.…”

“…We have previously applied gene-based testing to analyze the association between AF susceptibility genes PITX2, KCNN3 , and ZFHX3 and left atrial diameter (LAD), AF type and AF recurrence after ablation. Among the three candidate genes, only ZFHX3 associated with LA dilatation and AF recurrence after catheter ablation (Husser et al, 2017 ).…”

Identification of Central Regulators of Calcium Signaling and ECM–Receptor Interaction Genetically Associated With the Progression and Recurrence of Atrial Fibrillation

“…Important candidates identified by other studies which are not part of calcium signaling and ECM–receptor interaction were beyond the focus of our study. PITX2 , ZFHX3 , and KCNN3 were analyzed in a single gene approach as recently published by our group ( Husser et al, 2017 ).…”

Study on the relationship between telomere length changes and recurrence of atrial fibrillation after radiofrequency catheter ablation

“…Given the invasive nature of RFCA, as well as the significant cost, the need for improved strategies to guide patient selection between ablative vs nonablative options is crucial . Several genome‐wide association studies regarding AF have reported that harboring common genetic variants could significantly increase AF recurrence rates . These genetic variants are mainly involved in inflammatory‐related pathways, which are related to the initiation and progression of AF by several mechanisms such as the promotion of structural remodeling of the left atrium .…”