Common VKORC1 and GGCX polymorphisms associated with warfarin dose View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-08

AUTHORS

M Wadelius, L Y Chen, K Downes, J Ghori, S Hunt, N Eriksson, O Wallerman, H Melhus, C Wadelius, D Bentley, P Deloukas

ABSTRACT

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. More... »

PAGES

262

Journal

TITLE

The Pharmacogenomics Journal

ISSUE

4

VOLUME

5

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.tpj.6500313

DOI

http://dx.doi.org/10.1038/sj.tpj.6500313

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031034545

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15883587


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