AT1 mutations and risk of atrial fibrillation based on genotypes from 71000 individuals from the general population

作者：Marott Sarah C W; Nordestgaard Borge G; Jensen Gorm B; Tybjaerg Hansen Anne; Benn Marianne^*

来源：British Journal of Clinical Pharmacology, 2013, 76(1): 114-124.

DOI：10.1111/bcp.12050

• AT1 gene
• atrial fibrillation
• epidemiology
• genetics

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.

• 出版日期2013-7