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Genetic variants associated with angiotensin-converting enzyme inhibitor-induced cough: a genome-wide association study in a Swedish population
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2017 (English)In: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 18, no 3, 201-213 p.Article in journal (Refereed) Published
Abstract [en]

Aim: We conducted a genome-wide association study on angiotensin-converting enzyme inhibitor-induced cough and used our dataset to replicate candidate genes iden-tified in previous studies. Patients & methods: A total of 124 patients and 1345 treated controls were genotyped using Illumina arrays. The genome-wide significance level was set to p < 5 x 10(-8). Results: We identified nearly genome-wide significant associations in CLASP1, PDE11A, KCNMB2, TGFA, SLC38A6 and MMP16. The strongest association was with rs62151109 in CLASP1 (odds ratio: 3.97; p = 9.44 x 10(-8)). All top hits except two were located in intronic or noncoding DNA regions. None of the candidate genes were significantly associated in our study. Conclusion: Angiotensin-converting enzyme inhibitor-induced cough is potentially associated with genes that are independent of bradykinin pathways.

Place, publisher, year, edition, pages
FUTURE MEDICINE LTD , 2017. Vol. 18, no 3, 201-213 p.
Keyword [en]
angiotensin converting enzyme inhibitors, bradykinin, cough, drug-related side effects and adverse reactions, enalapril, genome-wide association study, lisinopril, pharmacogenetics, quinapril, ramipril
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-318602DOI: 10.2217/pgs-2016-0184ISI: 000393682600002PubMedID: 28084903OAI: oai:DiVA.org:uu-318602DiVA: diva2:1086017
Funder
Swedish Research Council, Medicine 521-2011-2440 521-2014-3370Swedish Heart Lung Foundation, 20120557 20140291Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2017-03-31Bibliographically approved

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Hallberg, PärPersson, MatildaAxelsson, TomasCavalli, MarcoJohansson, Hans-ErikWadelius, ClaesEriksson, NiclasWadelius, Mia
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Clinical pharmacogenomics and osteoporosisScience for Life Laboratory, SciLifeLabMolecular MedicineMedicinsk genetik och genomikGeriatricsUCR-Uppsala Clinical Research Center
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