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. 2017 Dec 19:8:224.
doi: 10.3389/fgene.2017.00224. eCollection 2017.

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

Daniela Husser  1 , Petra Büttner  1 , Dorian Stübner  1 , Laura Ueberham  1   2 , Pyotr G Platonov  3 , Borislav Dinov  1 , Arash Arya  1 , Gerhard Hindricks  1   2 , Andreas Bollmann  1   2
Affiliations

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

Daniela Husser et al. Front Genet. .

Abstract

Background: PR interval prolongation has recently been shown to associate with advanced left atrial remodeling and atrial fibrillation (AF) recurrence after catheter ablation. While different genome-wide association studies (GWAS) have implicated 13 loci to associate with the PR interval as an AF endophenotype their subsequent associations with AF remodeling and response to catheter ablation are unknown. Here, we perform a gene-based analysis of GWAS data to test the hypothesis that PR interval candidate genes also associate with left atrial remodeling and arrhythmia recurrence following AF catheter ablation. Methods and Results: Samples 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 VEGAS (versatile gene-based association study). Among the 13 candidate genes, SLC8A1, MEIS1, ITGA9, SCN5A, and SOX5 associated with the PR interval. Of those, ITGA9 and SOX5 were significantly associated with left atrial low voltage areas and left atrial diameter and subsequently with AF recurrence after radiofrequency catheter ablation. Conclusion: This study suggests contributions of ITGA9 and SOX5 to AF remodeling expressed as PR interval prolongation, low voltage areas and left atrial dilatation and subsequently to response to catheter ablation. Future and larger studies are necessary to replicate and apply these findings with the aim of designing AF pathophysiology-based multi-locus risk scores.

Keywords: PR interval; atrial fibrillation; catheter ablation; gene-based analysis; genome wide association study.

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Figures

Figure 1
Figure 1
Regional association plot for all significant ITGA9 (left) and SOX5 (right) SNPs and response to AF ablation. The plot was created using GWAS association data that served as the input for gene-based testing. The x-axis represents the distribution of SNPs across the genes while the y-axis represents the −log10 of the P-value of each SNP in the gene. The colors indicate the r2 between the SNP with the lowest P-value and all the other SNPs. The light blue trace indicates recombination hotspots.
See this image and copyright information in PMC

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