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- Title
AT<sub>1</sub> mutations and risk of atrial fibrillation based on genotypes from 71 000 individuals from the general population.
- Authors
Marott, Sarah C. W.; Nordestgaard, Børge G.; Jensen, Gorm B.; Tybjærg‐Hansen, Anne; Benn, Marianne
- Abstract
Aims Activation of the angiotensin II type 1 (AT1) receptor has been shown to mediate the structural and electrical remodelling of the atrial myocardium associated with atrial fibrillation. We hypothesized that AT1 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 AT1 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 AT1 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 AT1 genetic variants A244 S and I103 T/ A244 S was associated with increased risk of atrial fibrillation in men. The AT1 recptor might be a target for the pharmaceutical industry. This finding needs to be validated in independent studies.
- Subjects
ANGIOTENSIN II; ATRIAL fibrillation; GENOTYPE-environment interaction; CARDIOMYOPATHIES; HYPERTENSION; CARDIOVASCULAR diseases risk factors
- Publication
British Journal of Clinical Pharmacology, 2013, Vol 76, Issue 1, p114
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/bcp.12050