Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain γ-carboxylation of vitamin K-dependent proteins. Two different phenotypes are associated with mutations in human VKORC1. The majority of mutations cause resistance to 4-hydroxycoumarin- and indandione-based vitamin K antagonists (VKA) used in the prevention an...

Studies assessing the impact of gene-environment interactions on common human diseases and traits have been relatively few for many reasons. One often acknowledged reason is that it is difficult to accurately measure the environment or exposure. Indeed, most large-scale epidemiologic studies use questionnaires to assess and measure past and current exposure levels. While questionnaires may be c...

Since the discovery of warfarin-sensitive vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1), 26 human VKORC1 (hVKORC1) missense mutations have been associated with oral anticoagulant resistance (OACR). Assessment of warfarin resistance using the "classical" dithiothreitol-driven vitamin K 2,3-epoxide reductase (VKOR) assay has not reflected clinical resistance phenotypes for most mutat...

We aimed to confirm the correlations between rs2359612 and rs9923231 single nucleotide polymorphisms (SNPs) in the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene and the risk of cardiovascular and cerebrovascular diseases (CCVDs) using meta-analysis. Electronic databases were exhaustively searched for relevant case-control studies by employing stringent inclusion and exclusion crit...

Inherited variants of the enzymes involved in drug metabolism, transporters, receptors may play an important role in drug response. Genotyping prior to drug administration seems to be a promising clinical approach in order to reduce the adverse effects of the drugs and to increase their efficacy. Oral anticoagulants (OAs) are drugs largely used in the prevention and treatment of thrombo-embolic...

A warfarin-resistant strain and a warfarin-susceptible strain of wild rats (Rattus norvegicus) maintained in enclosures of the National Veterinary School of Lyon (France) were studied to determine the mechanism of the resistance to anticoagulant rodenticides. A low vitamin K epoxide reductase (VKOR) activity has been reported for many resistant rat strains. As recently suggested, mutations in t...

Thromb Haemost 2008; 100: 175–176 More than 60 years after its successful introduction for the prevention of thromboembolic events, the coumarin anticoagulant warfarin is still one of the most frequently prescribed cardiovascular drugs. The recently conducted Active W study once again established its therapeutic superiority over even a combination of antiplatelet drugs for the prevention of str...

Aim To evaluate applicability of CYP2C9*2, *3 and VKORC1-1639G > A based algorithm to predict warfarin stable dose (WSD) in a group of Palestinian patients. Patients & methods Warfarin doses were retrospectively calculated for 101 Palestinian patients under warfarin therapy using three models. Performance of the three models was assessed in 47 patients found to take WSD. Results Frequency o...