Details

Autor(en) / Beteiligte

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

Titel

Common VKORC1 and GGCX polymorphisms associated with warfarin dose

Ist Teil von

• The pharmacogenomics journal, 2005-01, Vol.5 (4), p.262-270

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2005

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.