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

Authors

  • Sarah C. W. Marott,

    1. Department of Clinical Biochemistry, Herlev Hospital, Herlev
    2. Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen
    Search for more papers by this author
  • Børge G. Nordestgaard,

    1. Department of Clinical Biochemistry, Herlev Hospital, Herlev
    2. Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen
    3. The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen
    Search for more papers by this author
  • Gorm B. Jensen,

    1. Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen
    2. The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen
    3. Department of Medicine, Hvidovre Hospital, Hvidovre
    Search for more papers by this author
  • Anne Tybjærg-Hansen,

    1. Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen
    2. The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen
    3. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
    Search for more papers by this author
  • Marianne Benn

    Corresponding author
    1. Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen
    • Department of Clinical Biochemistry, Herlev Hospital, Herlev
    Search for more papers by this author

Correspondence

Dr Marianne Benn MD, PhD, DMSc, Department of Clinical Biochemistry, Gentofte Hospital, Niels Andersens vej 65, DK-2900 Hellerup, Denmark.

Tel.: +45 3977 7494

Fax: +45 3977 7616

E-mail: marianne.benn@regionh.dk

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 (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.

Ancillary