Identification of the gene for vitamin K epoxide reductase

@article{Li2004IdentificationOT,
  title={Identification of the gene for vitamin K epoxide reductase},
  author={Tao Li and Chun-Yun Chang and D Y Jin and P J Lin and Anastasia Khvorova and Darrel W Stafford},
  journal={Nature},
  year={2004},
  volume={427},
  pages={541-544}
}
Vitamin K epoxide reductase (VKOR) is the target of warfarin, the most widely prescribed anticoagulant for thromboembolic disorders. Although estimated to prevent twenty strokes per induced bleeding episode, warfarin is under-used because of the difficulty of controlling dosage and the fear of inducing bleeding. Although identified in 1974 (ref. 2), the enzyme has yet to be purified or its gene identified. A positional cloning approach has become possible after the mapping of warfarin… 

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The biochemical and cell biological evidence suggests that hVKOR has a distinct fold from its ancestral protein, though the single nucleotide polymorphisms used in personalized medicine strategies for warfarin dosing should be carefully considered.
Structural and functional insights into human vitamin K epoxide reductase and vitamin K epoxide reductase-like1
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  • Biology
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  • 2013
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Results presented here underline the need of VKORC1 haplotyping in anticoagulated patients with unusual clinical antICOagulant response, and the examination can have further therapeutic consequences.
Presence of a T383G Mutation in the Vitamin K Epoxide Reductase Gene (VKORC1) in a Patient Resistant to Four Different Vitamin K Antagonists.
TLDR
A resistance to all vitamin K antagonists, including warfarin up to 45 mg/day is extremely rare and the mutation T383G of the VKORC gene has been reported in only one patient before the case reported here.
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This is the first documented Irish case of true warfarin resistance as a result of a mutation in VKORC1, a novel gene encoding a component of the epoxide reductase enzyme complex which is an essential component in the recycling pathway of vitamin K and is postulated to be one of the sites of action of warfarins.
VKORC1 pharmacogenomics summary.
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A number of large-scale randomized clinical trials are now in progress to develop a globally applicable dosing strategy for warfarin, and it is shown that polymorphisms in the VKORC1 gene were associated with both high and low-warfarin dose phenotypes in humans.
VKORC1: molecular target of coumarins
TLDR
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A novel mutation in VKORC1 and its effect on enzymatic activity in Japanese warfarin-resistant rats.
TLDR
The mechanism underlying warfarin resistance is clarified, and a novel substitution of arginine to proline at position 33 of the VKORC1 amino acid sequence is identified, which helps clarify how these rats can survive with a markedly reduced VKOR activity and how they simultaneously exhibit warFarin resistance.
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