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Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.ORCID iD: 0000-0002-6368-2622
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. (Systems genomics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Osteoporos)
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2004 (English)In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 4, no 1, 40-8 p.Article in journal (Refereed) Published
Abstract [en]

The required dose of the oral anticoagulant warfarin varies greatly, and overdosing often leads to bleeding. Warfarin is metabolised by cytochrome P450 enzymes CYP2C9, CYP1A2 and CYP3A. The target cell level of warfarin may be dependent on the efflux pump P-glycoprotein, encoded by the adenosine triphosphate-binding cassette gene ABCB1 (multidrug resistance gene 1). Genetic variability in CYP2C9, CYP3A5 and ABCB1 was analysed in 201 stable warfarin-treated patients using solid-phase minisequencing, pyrosequencing and SNaPshot. CYP2C9 variants, age, weight, concurrent drug treatment and indication for treatment significantly influenced warfarin dosing in these patients, explaining 29% of the variation in dose. CYP3A5 did not affect warfarin dosing. An ABCB1 haplotype containing the exon 26 3435T variant was over-represented among low-dose patients. Thirty-six patients with serious bleeding complications had higher prothrombin time international normalised ratios than 189 warfarin-treated patients without serious bleeding, but there were no significant differences in CYP2C9, CYP3A5 or ABCB1 genotypes and allelic variants.

Place, publisher, year, edition, pages
2004. Vol. 4, no 1, 40-8 p.
Keyword [en]
warfarin, pharmacogenetics, CYP2C9, CYP3A5, ABCB1
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-65315DOI: 10.1038/sj.tpj.6500220PubMedID: 14676821OAI: oai:DiVA.org:uu-65315DiVA: diva2:93226
Available from: 2008-01-18 Created: 2008-01-18 Last updated: 2017-11-30

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Wadelius, MiaWallerman, OlaWadelius, ClaesMelhus, Håkan

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Clinical pharmacogenomics and osteoporosisClinical PharmacologyDepartment of Genetics and PathologyDepartment of Medical Sciences
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