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Brugada syndrome risk loci seem protective against atrial fibrillation.

ABSTRACT: Several studies have shown an overlap between genes involved in the pathophysiological mechanisms of atrial fibrillation (AF) and Brugada Syndrome (BrS). We investigated whether three single-nucleotide polymorphisms (SNPs) (rs11708996; G>C located intronic to SCN5A, rs10428132; T>G located in SCN10A, and rs9388451; T>C located downstream to HEY2) at loci associated with BrS in a recent genome-wide association study (GWAS) also were associated with AF. A total of 657 patients diagnosed with AF and a control group comprising 741 individuals free of AF were included. The three SNPs were genotyped using TaqMan assays. The frequencies of risk alleles in the AF population and the control population were compared in two-by-two models. One variant, rs10428132 at SCN10A, was associated with a statistically significant decreased risk of AF (odds ratio (OR)=0.77, P=0.001). A meta-analysis was performed by enriching the control population with allele frequencies from controls in the recently published BrS GWAS (2230 alleles). In this meta-analysis, both rs10428132 at SCN10A (OR=0.73, P=5.7 × 10(-6)) and rs11708996 at SCN5A (OR=0.80, P=0.02) showed a statistically significant decreased risk of AF. When assessing the additive effect of the three loci, we found that the risk of AF decreased in a dose-responsive manner with increasing numbers of risk alleles (OR=0.50, P=0.001 for individuals carrying ?4 risk alleles vs ?1 allele). In conclusion, the prevalence of three risk alleles previously associated with BrS was lower in AF patients than in patients free of AF, suggesting a protective role of these loci in developing AF.

SUBMITTER: Andreasen L

PROVIDER: S-EPMC4231412 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Brugada syndrome risk loci seem protective against atrial fibrillation.

Andreasen Laura L Nielsen Jonas B JB Darkner Stine S Christophersen Ingrid E IE Jabbari Javad J Refsgaard Lena L Thiis Jens J JJ Sajadieh Ahmad A Tveit Arnljot A Haunsø Stig S Svendsen Jesper H JH Schmitt Nicole N Olesen Morten S MS

European journal of human genetics : EJHG 20140326 12

Several studies have shown an overlap between genes involved in the pathophysiological mechanisms of atrial fibrillation (AF) and Brugada Syndrome (BrS). We investigated whether three single-nucleotide polymorphisms (SNPs) (rs11708996; G>C located intronic to SCN5A, rs10428132; T>G located in SCN10A, and rs9388451; T>C located downstream to HEY2) at loci associated with BrS in a recent genome-wide association study (GWAS) also were associated with AF. A total of 657 patients diagnosed with AF an ...[more]

PMID: 24667784

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Brugada syndrome risk loci seem protective against atrial fibrillation.

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Brugada syndrome risk loci seem protective against atrial fibrillation.

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