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PR interval associated genes, atrial remodeling and rhythm outcome of catheter ablation of atrial fibrillation-A gene-based analysis of GWAS data

Husser, Daniela ; Büttner, Petra ; Stübner, Dorian ; Ueberham, Laura ; Platonov, Pyotr G. LU ; Dinov, Borislav ; Arya, Arash ; Hindricks, Gerhard and Bollmann, Andreas LU (2017) In Frontiers in Genetics 8(DEC).
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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atrial fibrillation, Catheter ablation, Gene-based analysis, Genome wide association study, PR interval
in
Frontiers in Genetics
volume
8
issue
DEC
article number
224
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85039939195
  • pmid:29312445
ISSN
1664-8021
DOI
10.3389/fgene.2017.00224
language
English
LU publication?
yes
id
a940e0ac-9cf7-437a-a398-63be012dc9af
date added to LUP
2018-01-22 16:19:28
date last changed
2024-04-15 01:06:47
@article{a940e0ac-9cf7-437a-a398-63be012dc9af,
  abstract     = {{<p>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.</p>}},
  author       = {{Husser, Daniela and Büttner, Petra and Stübner, Dorian and Ueberham, Laura and Platonov, Pyotr G. and Dinov, Borislav and Arya, Arash and Hindricks, Gerhard and Bollmann, Andreas}},
  issn         = {{1664-8021}},
  keywords     = {{Atrial fibrillation; Catheter ablation; Gene-based analysis; Genome wide association study; PR interval}},
  language     = {{eng}},
  number       = {{DEC}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Genetics}},
  title        = {{PR interval associated genes, atrial remodeling and rhythm outcome of catheter ablation of atrial fibrillation-A gene-based analysis of GWAS data}},
  url          = {{http://dx.doi.org/10.3389/fgene.2017.00224}},
  doi          = {{10.3389/fgene.2017.00224}},
  volume       = {{8}},
  year         = {{2017}},
}