Association of Variants Near the Bradykinin Receptor B
ACE inhibitors
ADR
adverse drug reaction
angioedema
bradykinin
bradykinin receptor B(2)
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
17 08 2021
17 08 2021
Historique:
received:
09
04
2021
revised:
06
05
2021
accepted:
18
05
2021
entrez:
13
8
2021
pubmed:
14
8
2021
medline:
18
12
2021
Statut:
ppublish
Résumé
Angioedema is a rare but potentially life-threatening adverse reaction associated with angiotensin-converting enzyme (ACE) inhibitors. Identification of potential genetic factors related to this adverse event may help identify at-risk patients. The aim of this study was to identify genetic factors associated with ACE inhibitor-associated angioedema. 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. 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 × 10 In this genomewide association study involving individuals treated with ACE inhibitors, we found that common variants located in close proximity to the bradykinin receptor B
Sections du résumé
BACKGROUND
Angioedema is a rare but potentially life-threatening adverse reaction associated with angiotensin-converting 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 × 10
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 B
Identifiants
pubmed: 34384552
pii: S0735-1097(21)05394-8
doi: 10.1016/j.jacc.2021.05.054
pii:
doi:
Substances chimiques
Angiotensin-Converting Enzyme Inhibitors
0
Receptor, Bradykinin B2
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
696-709Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support and Author Disclosures This work was supported by the John and Birthe Meyer Foundation, the Research Foundation at Rigshospitalet, the Innovation Fund Denmark (PM Heart), NordForsk, the Villadsen Family Foundation (Copenhagen, Denmark), the Arvid Nilsson Foundation (Copenhagen, Denmark), the Hallas-Møller Emerging Investigator Novo Nordisk (NNF17OC0031204; Copenhagen, Denmark), the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001; Copenhagen, Denmark), the Swedish Research Council (Medicine 521-2011-2440, 521-2014-3370, and 2018-03307; Uppsala, Sweden), the Swedish Heart and Lung Foundation (20120557, 20140291, and 20170711; Uppsala, Sweden), the Medical Products Agency (Uppsala, Sweden), Selander’s Foundation (Uppsala, Sweden), and Thureus’ Foundation and Clinical Research Support “Avtal om Läkarutbildning och Forskning” (Uppsala, Sweden). The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under grant 2017-00641. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.