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Exome Sequencing Reveals Common and Rare Variants in F5 Associated With ACE Inhibitor and Angiotensin Receptor Blocker–Induced Angioedema
Open accessAbstract
Angioedema occurring in the head and neck region is a rare and sometimes life‐threatening adverse reaction to angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Few studies have investigated the association of common variants with this extreme reaction, but none have explored the combined influence of rare variants yet. Adjudicated cases of ACEI‐induced angioedema (ACEI‐AE) or ARB‐induced angioedema (ARB‐AE) and controls were recruited at five different centers. Sequencing of 1,066 samples (408 ACEI‐AE, ARB‐AE, and 658 controls) was performed using exome‐enriched sequence data. A common variant of the F5 gene that causes an increase in blood clotting (rs6025, p.Arg506Gln, also called factor V Leiden), was significantly associated with both ACEI‐AE and ARB‐AE (odds ratio: 2.85, 95% confidence interval (CI), 1.89–4.25). A burden test analysis of five rare missense variants in F5 was also found to be associated with ACEI‐AE or ARB‐AE, P = 2.09 × 10−3. A combined gene risk score of these variants, and the common variants rs6025 and rs6020, showed that individuals carrying at least one variant had 2.21 (95% CI, 1.49–3.27, P = 6.30 × 10−9) times the odds of having ACEI‐AE or ARB‐AE. The increased risk due to the common Leiden allele was confirmed in a genome‐wide association study from the United States. A high risk of angioedema was also observed for the rs6020 variant that is the main coagulation defect‐causing variant in black African and Asian populations. We found that deleterious missense variants in F5 are associated with an increased risk of ACEI‐AE or ARB‐AE.
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A recent exome study implicated the coagulation system in ACEi-AE by demonstrating an association with variants in the F5 gene, in particular the factor V Leiden mutation.
“By demonstrating an association with variants in the F5 gene, in particular the factor V Leiden mutation, a recent exome study implicated the coagulation system in ACEi-AE.17”
From Meta-analysis of ACE inhibitor-induced angioedema identifies novel risk locus. (2024) · cites this paper as [17]
The 1q24.2 locus was first reported by Maroteau et al albeit at the level of exome-wide significance only.
“The 1q24.2 locus was first reported by Maroteau et al 17 albeit at the level of exome-wide significance only (P < 1 3 10 6 ).”
From Meta-analysis of ACE inhibitor-induced angioedema identifies novel risk locus. (2024) · cites this paper as [17]
The coding variant rs6025 was reported as the top SNP at the 1q24.2 locus in the previous exome-sequencing study and represents a variant largely independent of rs6687813 (r2 = 0.172).
“This was reported as the top SNP at this locus in the previous exome-sequencing study 17 and represents a variant that is largely independent of rs6687813 (r 2 5 0.172).”
From Meta-analysis of ACE inhibitor-induced angioedema identifies novel risk locus. (2024) · cites this paper as [17]
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Brown, N. J., Ray, W. A., Snowden, M., & Griffin, M. R. (1996) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(96)90161-7 · Cited by 313
Self-citationDuan, Q. L., Nikpoor, B., Dubé, M.-P., Molinaro, G., Meijer, I. A., Dion, P., Rochefort, D., Saint-Onge, J., Flury, L., Brown, N. J., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/496899 · Cited by 126
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Research works printed but not linked: 35
- 10.2174/1381612820666141112160013 · DOI
- 10.1016/j.ehj.2004.06.003 · DOI
- 10.1161/01.CIR.98.21.2358 · DOI
- 10.1111/joim.12867 · DOI
- 10.1016/j.otohns.2008.03.029 · DOI
- 10.1161/HYPERTENSIONAHA.108.111393 · DOI
- 10.1038/clpt.2014.138 · DOI
- 10.1038/clpt.2014.121 · DOI · Paper page
- 10.1093/eurheartj/ehx467 · DOI
- 10.1016/j.clinthera.2017.05.235 · DOI
- Rasmussen E.R., 2020, Genome‐wide association study of angioedema induced by angiotensin‐converting enzyme inhibitor and angiotensin receptor blocker treatment.
- 10.1097/FPC.0b013e328363c137 · DOI
- Gibbs C.R., 1999, Angioedema due to ACE inhibitors: increased risk in patients of African origin, Br. J. Clin. Pharmacol., 48, 861–865, 10.1046/j.1365-2125.1999.00093.x · DOI
- 10.1155/2017/1476402 · DOI
- 10.1111/fcp.12313 · DOI
- 10.1177/1060028016682251 · DOI
- 10.1038/s41397-020-0148-3 · DOI
- 10.1136/bmjopen-2016-013351 · DOI
- 10.1017/thg.2012.104 · DOI
- Baranova E.V., 2018, Genome‐wide association study of angiotensin‐converting‐enzyme (ACE) inhibitor‐induced angioedema imputed to the Haplotype Reference Consortium panel, Precision Med.
- 10.1093/bioinformatics/btr330 · DOI
- 10.1093/bioinformatics/btw079 · DOI
- 10.1093/biostatistics/kxs014 · DOI
- 10.1016/j.ajhg.2008.06.024 · DOI · Paper page
- 10.1186/1471-2105-11-288 · DOI
- 10.18637/jss.v036.i03 · DOI · Paper page
- The R Development Core Team, 2007, R: A Language and Environment for Statistical Computing
- 10.2337/dc13-1995 · DOI
- 10.1086/509899 · DOI
- 10.1124/jpet.103.064105 · DOI · Paper page
- 10.1016/j.iac.2006.08.001 · DOI · Paper page
- 10.3389/fmed.2017.00206 · DOI
- 10.1038/369064a0 · DOI
- 10.1160/TH06-01-0062 · DOI
- 10.1371/journal.pone.0104461 · DOI
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Ghouse, J., Ahlberg, G., Andreasen, L., Banasik, K., Brunak, S., Schwinn, M., Larsen, I. H., Petersen, O., Sørensen, E., Ullum, H., et al. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.05.054 · Cited by 24
Self-citationMeta-analysis of ACE inhibitor-induced angioedema identifies novel risk locus.
Mathey, C. M., Maj, C., Eriksson, N., Krebs, K., Westmeier, J., David, F. S., Koromina, M., Scheer, A. B., Szabo, N., Wedi, B., et al. (2024) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2023.11.921 · Cited by 15
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Metadata
- Authors
- Maroteau, C., Siddiqui, M. K., Veluchamy, A., Carr, F., White, M., Cassidy, A. J., Baranova, E. V., Rasmussen, E. R., Eriksson, N., Bloch, K. M., Brown, N. J., Bygum, A., Hallberg, P., Karawajczyk, M., Magnusson, P. K. E., Yue, Q., Syvänen, A., von Buchwald, C., Alfirevic, A., Maitland‐van der Zee, A. H., Wadelius, M., Palmer, C. N. A., & PREDICTION‐ADR
- Affiliations
- University of Dundee (GB)
- Utrecht University (NL)
- University of Copenhagen (DK)
- Uppsala University (SE)
- University of Liverpool (GB)
- Vanderbilt University Medical Center (US)
- Odense University Hospital (DK)
- Department of Medical Sciences Clinical Pharmacology and Science for Life Laboratory Uppsala University Uppsala Sweden
- Karolinska Institutet (SE)
- Uppsala Monitoring Centre (SE)
- Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University Utrecht The Netherlands
- Corresponding author
- Maroteau, Cyrielle
- ORCID
- Maroteau, Cyrielle
- Siddiqui, Moneeza Kalhan
- Veluchamy, Abirami
- Cassidy, Andrew J.
- Baranova, Ekaterina V.
- Rasmussen, Eva R.
- Eriksson, Niclas
- Brown, Nancy J.
- Bygum, Anette
- Hallberg, Par
- Karawajczyk, Malgorzata
- Magnusson, Patrik K. E.
- Yue, Qun‐Ying
- Syvänen, Ann‐Christine
- von Buchwald, Christian
- Alfirevic, Ana
- Wadelius, Mia
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2020-07-18
- Volume
- 108
- Issue
- 6
- Pages
- 1195-1202
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- PMC
- PMC10306231
- OpenAlex
- W3031020182
- Cited by
- 21
- References
- 2
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, cc-by-nc)
- PubMed Central (acceptedVersion, cc-by-nc)
- Discovery Research Portal (University of Dundee) (submittedVersion, cc-by-nc)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Funders
- University of Dundee (2017‐00641,)
- Universitetssjukhuset Örebro
- Örebro Universitet
- Odense Universitetshospital
- Karolinska Institutet
- Uppsala Universitet
- Universitair Medisch Centrum Utrecht
- Topics
- Health Sciences › Medicine › Hematology › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- F5 gene, factor V Leiden, ACE inhibitor-induced angioedema, drug-induced angioedema, rare missense variants, burden test, adverse drug reactions, coagulation defects, pharmacogenetics
- MeSH terms
- Exome Sequencing, Aged, Angioedema, Angiotensin-Converting Enzyme Inhibitors, DNA Mutational Analysis, Europe, Factor V, Female, Humans, Male, Middle Aged, Risk Factors, United States, Case-Control Studies, Risk Assessment, Genetic Predisposition to Disease, Mutation, Missense, Genome-Wide Association Study, Angiotensin Receptor Antagonists, Exome, Mutation Rate
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