Brugada syndrome risk loci seem protective against atrial fibrillation
| Autor: | Laura Andreasen, Javad Jabbari, Arnljot Tveit, Stine Darkner, Lena Refsgaard, Jonas B. Nielsen, Ingrid E. Christophersen, Jesper Hastrup Svendsen, Morten S. Olesen, Ahmad Sajadieh, Nicole Schmitt, Thiis Jj, Stig Haunsø |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Genotyping Techniques Population Genome-wide association study Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Gastroenterology Article Young Adult Gene Frequency Risk Factors Internal medicine Atrial Fibrillation Genetics medicine Humans Genetic Predisposition to Disease Allele education Allele frequency Alleles Genetics (clinical) Aged Brugada Syndrome Brugada syndrome education.field_of_study Atrial fibrillation Odds ratio Middle Aged medicine.disease Logistic Models Genetic Loci Case-Control Studies Female Genome-Wide Association Study |
| Zdroj: | European Journal of Human Genetics. 22:1357-1361 |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/ejhg.2014.46 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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