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Association of Vari...
Association of Variants Near the Bradykinin Receptor B2 Gene With Angioedema in Patients Taking ACE Inhibitors
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- Ghouse, Jonas (author)
- Rigshosp, Copenhagen Univ Hosp, Lab Mol Cardiol, Dept Cardiol, Bldg 9312,Juliane Maries Vej 20, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Lab Mol Cardiol, Dept Biomed Sci, Copenhagen, Denmark.
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- Ahlberg, Gustav (author)
- Rigshosp, Copenhagen Univ Hosp, Lab Mol Cardiol, Dept Cardiol, Bldg 9312,Juliane Maries Vej 20, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Lab Mol Cardiol, Dept Biomed Sci, Copenhagen, Denmark.
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- Andreasen, Laura (author)
- Rigshosp, Copenhagen Univ Hosp, Lab Mol Cardiol, Dept Cardiol, Bldg 9312,Juliane Maries Vej 20, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Lab Mol Cardiol, Dept Biomed Sci, Copenhagen, Denmark.
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- Banasi, Karina (author)
- Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Translat Dis Syst Biol, Copenhagen, Denmark.
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- Brunak, Soren (author)
- Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Translat Dis Syst Biol, Copenhagen, Denmark.
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- Schwinn, Michael (author)
- Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark.
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- Larsen, Ina Holst (author)
- Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark.
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- Petersen, Oscar (author)
- Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark.
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- Sorensen, Erik (author)
- Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark.
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- Ullum, Henrik (author)
- Statens Serum Inst, Copenhagen, Denmark.
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- Rasmussen, Eva Rye (author)
- Univ Copenhagen, Rigshosp, Dept Otorhinolaryngol Head & Neck Surg & Audiol, DK-2100 Copenhagen, Denmark.
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- Eriksson, Niclas, 1978- (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)
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- Hallberg, Pär, 1974- (author)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
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- Wadelius, Mia (author)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab
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- Bundgaard, Henning (author)
- Univ Copenhagen, Rigshosp, Copenhagen Univ Hosp, Dept Cardiol, DK-2100 Copenhagen, Denmark.
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- Olesen, Morten S. (author)
- Rigshosp, Copenhagen Univ Hosp, Lab Mol Cardiol, Dept Cardiol, Bldg 9312,Juliane Maries Vej 20, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Lab Mol Cardiol, Dept Biomed Sci, Copenhagen, Denmark.
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Rigshosp, Copenhagen Univ Hosp, Lab Mol Cardiol, Dept Cardiol, Bldg 9312,Juliane Maries Vej 20, DK-2100 Copenhagen, Denmark;Univ Copenhagen, Lab Mol Cardiol, Dept Biomed Sci, Copenhagen, Denmark. Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Translat Dis Syst Biol, Copenhagen, Denmark. (creator_code:org_t)
- Elsevier, 2021
- 2021
- English.
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In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 78:7, s. 696-709
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- BACKGROUND Angioedema is a rare but potentially life-threatening adverse reaction associated with angiotensinconverting enzyme (ACE) inhibitors. Identification of potential genetic factors related to this adverse event may help identify at-risk patients. OBJECTIVES The aim of this study was to identify genetic factors associated with ACE inhibitor-associated angioedema. METHODS A genomewide association study involving patients of European descent, all taking ACE inhibitors, was conducted in a discovery cohort (Copenhagen Hospital Biobank), and associations were confirmed in a replication cohort (Swedegene). Cases were defined as subjects with angioedema events and filled prescriptions for ACE inhibitors #180 days before the events. Control subjects were defined as those with continuous treatment with ACE inhibitors without any history of angioedema. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for angioedema risk using logistic mixed model regression analysis. Summary statistics from the discovery and replication cohorts were analyzed using a fixed-effects meta-analysis model. RESULTS The discovery cohort consisted of 462 cases and 53,391 ACE inhibitor-treated control subjects. The replication cohort consisted of 142 cases and 1,345 ACE inhibitor-treated control subjects. In the discovery cohort, 1 locus, residing at chromosome 14q32.2, was identified that associated with angioedema at the genomewide significance level of P <5 x 10-8. The lead variant at this locus, rs34485356, is an intergenic variant located 60 kb upstream of BDKRB2 (OR: 1.62; 95% CI: 1.38 to 1.90; P = 4.3 x 10-9). This variant was validated in our replication cohort with a similar direction and effect size (OR: 1.60; 95% CI: 1.13 to 2.25; P = 7.2 x 10-3). We found that carriers of the risk allele had significantly lower systolic (-0.46 mm Hg per T allele; 95% CI:-0.83 to-0.10; P = 0.013) and diastolic (-0.26 mm Hg per T allele; 95% CI:-0.46 to-0.05; P = 0.013) blood pressure. CONCLUSIONS In this genomewide association study involving individuals treated with ACE inhibitors, we found that common variants located in close proximity to the bradykinin receptor B2 gene were associated with increased risk for ACE inhibitor-related angioedema.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- ACE inhibitors
- ADR
- angioedema
- bradykinin
- adverse drug 
- reaction
- bradykinin 
- receptor B < sub > 2 <
- sub >
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ghouse, Jonas
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Ahlberg, Gustav
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Andreasen, Laura
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Banasi, Karina
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Brunak, Soren
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Schwinn, Michael
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Larsen, Ina Hols ...
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Petersen, Oscar
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Sorensen, Erik
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Ullum, Henrik
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Rasmussen, Eva R ...
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Eriksson, Niclas ...
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Hallberg, Pär, 1 ...
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Wadelius, Mia
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Bundgaard, Henni ...
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Olesen, Morten S ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Uppsala University