title: AT1 mutations and risk of atrial fibrillation based on genotypes from 71,000 individuals from the general population.
abstract: OBJECTIVE
  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 (I103T and A244S), 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 A244S and I103T/A244S 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 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.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark.
authors.forename: Sarah C W
authors.initials: SC
authors.lastname: Marott
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Gorm B
authors.initials: GB
authors.lastname: Jensen
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjaerg-Hansen
authors.forename: Marianne
authors.initials: M
authors.lastname: Benn
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics*; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012306:Risk; D012737:Sex Factors
chemical_list: D044140:Receptor, Angiotensin, Type 1