AT1 mutations and risk of atrial fibrillation based on genotypes from 71,000 individuals from the general population

TY - JOUR

T1 - AT1 mutations and risk of atrial fibrillation based on genotypes from 71,000 individuals from the general population

AU - Marott, S C W

AU - Nordestgaard, B G

AU - Jensen, G B

AU - Tybjaerg-Hansen, A

AU - Benn, M

N1 - © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

PY - 2013/7

Y1 - 2013/7

N2 - Aims: Activation of the angiotensinII type1 (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 (I103T and A244S), which were subsequently genotyped in the prospective Copenhagen City Heart Study (n = 10603) and the prospective Copenhagen General Population Study (n = 60647). Results: Risk of atrial fibrillation for heterozygotes for AT1 genetic variants A244S and I103T/A244Svs. 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 A244S and I103T/A244S 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.

AB - Aims: Activation of the angiotensinII type1 (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 (I103T and A244S), which were subsequently genotyped in the prospective Copenhagen City Heart Study (n = 10603) and the prospective Copenhagen General Population Study (n = 60647). Results: Risk of atrial fibrillation for heterozygotes for AT1 genetic variants A244S and I103T/A244Svs. 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 A244S and I103T/A244S 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.

U2 - 10.1111/bcp.12050

DO - 10.1111/bcp.12050

M3 - Journal article

C2 - 23210602

SN - 0264-3774

SP - Epub ahead of print

JO - British Journal of Clinical Pharmacology, Supplement

JF - British Journal of Clinical Pharmacology, Supplement

ER -