Pharmacogenetics of target genes across the warfarin pharmacological pathway.

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Lal S, Jada SR, Xiang X, Lim WT, Lee EJ, Chowbay B

Pharmacogenetics of target genes across the warfarin pharmacological pathway.

Clin Pharmacokinet. 2006;45(12):1189-200.

PubMed ID

17112295 [ View in PubMed

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Abstract

Warfarin is a widely prescribed anticoagulant for thromboembolic disorders and exhibits wide inter-individual differences in its pharmacodynamic effects. Warfarin exerts its anticoagulant effect by inhibiting the enzymatic activity of vitamin K 2,3-epoxide reductase complex, subunit 1 (VKORC1) which regenerates reduced vitamin K as an essential cofactor for the post-translational gamma-carboxylation of glutamic acid residues on coagulation factors II, VII, IX and X, and the anticoagulant proteins C, S and Z. Recent studies have shown polymorphisms in genes involved in the uptake of vitamin K (apolipoprotein E [ApoE]), reduction of vitamin K 2,3-epoxide (VKORC1), metabolism of warfarin (cytochrome P450 2C9 [CYP2C9]), and gamma carboxylation (gamma-glutamyl carboxylase [GGCX]) to influence the pharmacokinetics and pharmacodynamics of warfarin in patients from different ethnic backgrounds, resulting in variable warfarin dose requirements. Understanding the causal relationship of these polygenic influences on warfarin dose requirements in patients of different ethnicity may be vital in reducing inter-patient variability and optimising anticoagulant therapy.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutamic acid	Vitamin K-dependent gamma-carboxylase	Protein	Humans	Unknown	Not Available	Details