Common VKORC1 and GGCX polymorphisms associated with warfarin dose
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and PathologyDepartment of Medical Sciences2005 (English)In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 5, no 4, 262-70 p.Article in journal (Refereed) Published
We report a novel combination of factors that explains almost 60% of variable response to warfarin. Warfarin is a widely used anticoagulant, which acts through interference with vitamin K epoxide reductase that is encoded by VKORC1. In the next step of the vitamin K cycle, gamma-glutamyl carboxylase encoded by GGCX uses reduced vitamin K to activate clotting factors. We genotyped 201 warfarin-treated patients for common polymorphisms in VKORC1 and GGCX. All the five VKORC1 single-nucleotide polymorphisms covary significantly with warfarin dose, and explain 29-30% of variance in dose. Thus, VKORC1 has a larger impact than cytochrome P450 2C9, which explains 12% of variance in dose. In addition, one GGCX SNP showed a small but significant effect on warfarin dose. Incorrect dosage, especially during the initial phase of treatment, carries a high risk of either severe bleeding or failure to prevent thromboembolism. Genotype-based dose predictions may in future enable personalised drug treatment from the start of warfarin therapy.The Pharmacogenomics Journal advance online publication, 10 May 2005; doi:10.1038/sj.tpj.6500313.
Place, publisher, year, edition, pages
2005. Vol. 5, no 4, 262-70 p.
warfarin, VKORC1, CYP2C9, pharmacogenomics, GGCX
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-72916DOI: 10.1038/sj.tpj.6500313PubMedID: 15883587OAI: oai:DiVA.org:uu-72916DiVA: diva2:100827