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




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Journal of Translational Medicine

, 15:71

Disease Biomarkers

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.

KeywordsAtrial fibrillation Catheter ablation Genome wide association study Gene-based analysis AbbreviationsAFatrial fibrillation

GWASgenome-wide association study-studies

LADleft atrial diameter

SNPsingle nucleotide polymorphism

Daniela Husser and Petra Büttner contributed equally to this work





Author: Daniela Husser - Petra Büttner - Laura Ueberham - Borislav Dinov - Philipp Sommer - Arash Arya - Gerhard Hindricks - Andre

Source: https://link.springer.com/



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