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AT 1 mutations and risk of atrial fibrillation based on genotypes from 71 000 individuals from the general population
Author(s) -
Marott Sarah C. W.,
Nordestgaard Børge G.,
Jensen Gorm B.,
TybjærgHansen Anne,
Benn Marianne
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12050
Subject(s) - atrial fibrillation , medicine , cardiology , population , confidence interval , prospective cohort study , nonsynonymous substitution , genotype , myocardial infarction , biology , genetics , gene , environmental health , genome
Aims Activation of the angiotensin II type 1 (AT 1 ) receptor has been shown to mediate the structural and electrical remodelling of the atrial myocardium associated with atrial fibrillation. We hypothesized that AT 1 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 1 gene in 760 individuals with atrial fibrillation and identified two nonsynonymous variants ( I 103 T and A 244 S ), which were subsequently genotyped in the prospective C openhagen C ity H eart S tudy ( n = 10 603) and the prospective C openhagen G eneral P opulation S tudy ( n = 60 647). Results Risk of atrial fibrillation for heterozygotes for AT 1 genetic variants A 244 S and I 103 T / A 244 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 1 genetic variants A 244 S and I 103 T / A 244 S was associated with increased risk of atrial fibrillation in men. The AT 1 recptor might be a target for the pharmaceutical industry. This finding needs to be validated in independent studies.