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AT1 mutations and risk of atrial fibrillation based on genotypes from 71 000 individuals from the general population.
- Source :
- British Journal of Clinical Pharmacology; Jul2013, Vol. 76 Issue 1, p114-124, 11p, 3 Diagrams, 1 Chart, 1 Graph
- Publication Year :
- 2013
-
Abstract
- Aims Activation of the angiotensin II type 1 (AT<subscript>1</subscript>) receptor has been shown to mediate the structural and electrical remodelling of the atrial myocardium associated with atrial fibrillation. We hypothesized that AT<subscript>1</subscript> genotypic variation is associated with atrial fibrillation or diseases predisposing to atrial fibrillation, such as hypertension, heart failure, ischaemic heart disease and myocardial infarction, in the general population. Methods We resequenced the AT<subscript>1</subscript> gene in 760 individuals with atrial fibrillation and identified two nonsynonymous variants ( I103 T and A244 S), which were subsequently genotyped in the prospective Copenhagen City Heart Study ( n = 10 603) and the prospective Copenhagen General Population Study ( n = 60 647). Results Risk of atrial fibrillation for heterozygotes for AT<subscript>1</subscript> genetic variants A244 S and I103 T/ A244 S vs. noncarriers was increased by 2.7-fold (95% confidence interval 1.5- to 5.1-fold) and 2.6-fold (95% confidence interval 1.6- to 4.2-fold), respectively, for men. Conclusions Heterozygosity for the nonsynonymous AT<subscript>1</subscript> genetic variants A244 S and I103 T/ A244 S was associated with increased risk of atrial fibrillation in men. The AT<subscript>1</subscript> recptor might be a target for the pharmaceutical industry. This finding needs to be validated in independent studies. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03065251
- Volume :
- 76
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- British Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 88287129
- Full Text :
- https://doi.org/10.1111/bcp.12050