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Gene Review

VKORC1  -  vitamin K epoxide reductase complex,...

Homo sapiens

Synonyms: EDTP308, IMAGE3455200, MST134, MST576, MSTP134, ...
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Disease relevance of VKORC1

  • METHODS AND RESULTS: To test the hypothesis, we studied the association of polymorphisms of VKORC1 with stroke (1811 patients), coronary heart disease (740 patients), and aortic dissection (253 patients) compared with matched controls (n=1811, 740, and 416, respectively) [1].
  • We hypothesized that VKORC1-dependent effects on the coagulation cascade and atherosclerosis would contribute to susceptibility for vascular diseases [1].
  • A number of factors such as patient age, body weight, co-morbidity, frailty, warfarin daily dose and CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the rate and extent of INR reversal [2].
  • We found that VKOR expression in arteries was prominent in vascular endothelial cells and was high in the ventricular aneurysm tissue of human heart and human fetal heart [3].

High impact information on VKORC1


Biological context of VKORC1


Anatomical context of VKORC1


Associations of VKORC1 with chemical compounds

  • Warfarin is a widely used anticoagulant, which acts through interference with vitamin K epoxide reductase that is encoded by VKORC1 [10].
  • 0. Genetic analyses for CYP2C9 (*2 and *3 alleles) and VKORC1 (-1639 polymorphism) were performed and venous INR and plasma R- and S-warfarin concentrations determined [11].
  • These individuals had normal vitamin-K dependent coagulation factor activities and undetectable serum PIVKAII and vitamin K1 2,3 epoxide suggesting that their basal vitamin K epoxide reductase activity was not adversely affected by the VKORC1 Val66Met substitution [12].
  • VKORC1 and CYP2C9 Genotypes and Phenprocoumon Anticoagulation Status: Interaction Between both Genotypes Affects Dose Requirement [13].
  • S- and R-warfarin concentrations, INR, and CYP2C9 and VKORC1 genotypes from 150 patients were used to develop a population pharmacokinetic/pharmacodynamic model in NONMEM [14].

Regulatory relationships of VKORC1


Other interactions of VKORC1


Analytical, diagnostic and therapeutic context of VKORC1


  1. VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection). Wang, Y., Zhang, W., Zhang, Y., Yang, Y., Sun, L., Hu, S., Chen, J., Zhang, C., Zheng, Y., Zhen, Y., Sun, K., Fu, C., Yang, T., Wang, J., Sun, J., Wu, H., Glasgow, W.C., Hui, R. Circulation (2006) [Pubmed]
  2. Appraisal of current vitamin K dosing algorithms for the reversal of over-anticoagulation with warfarin: the need for a more tailored dosing regimen. Sconce, E.A., Kamali, F. Eur. J. Haematol. (2006) [Pubmed]
  3. Vitamin k epoxide reductase: a protein involved in angiogenesis. Wang, Y., Zhen, Y., Shi, Y., Chen, J., Zhang, C., Wang, X., Yang, X., Zheng, Y., Liu, Y., Hui, R. Mol. Cancer Res. (2005) [Pubmed]
  4. PharmGKB Submission Update: VIII. PBAT Submission of Genetic Variation in VKORC1 to the PharmGKB Network. Gage, B.F., Eby, C.S. Pharmacol. Rev. (2006) [Pubmed]
  5. Vitamin K epoxide reductase: homology, active site and catalytic mechanism. Goodstadt, L., Ponting, C.P. Trends Biochem. Sci. (2004) [Pubmed]
  6. Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2. Chu, P.H., Huang, T.Y., Williams, J., Stafford, D.W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Bodin, L., Verstuyft, C., Tregouet, D.A., Robert, A., Dubert, L., Funck-Brentano, C., Jaillon, P., Beaune, P., Laurent-Puig, P., Becquemont, L., Loriot, M.A. Blood (2005) [Pubmed]
  8. Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin. Rost, S., Fregin, A., Hünerberg, M., Bevans, C.G., Müller, C.R., Oldenburg, J. Thromb. Haemost. (2005) [Pubmed]
  9. Membrane topology mapping of vitamin K epoxide reductase by in vitro translation/cotranslocation. Tie, J.K., Nicchitta, C., von Heijne, G., Stafford, D.W. J. Biol. Chem. (2005) [Pubmed]
  10. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Wadelius, M., Chen, L.Y., Downes, K., Ghori, J., Hunt, S., Eriksson, N., Wallerman, O., Melhus, H., Wadelius, C., Bentley, D., Deloukas, P. Pharmacogenomics J. (2005) [Pubmed]
  11. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Sconce, E.A., Khan, T.I., Wynne, H.A., Avery, P., Monkhouse, L., King, B.P., Wood, P., Kesteven, P., Daly, A.K., Kamali, F. Blood (2005) [Pubmed]
  12. Pharmacodynamic resistance to warfarin associated with a Val66Met substitution in vitamin K epoxide reductase complex subunit 1. Harrington, D.J., Underwood, S., Morse, C., Shearer, M.J., Tuddenham, E.G., Mumford, A.D. Thromb. Haemost. (2005) [Pubmed]
  13. VKORC1 and CYP2C9 Genotypes and Phenprocoumon Anticoagulation Status: Interaction Between both Genotypes Affects Dose Requirement. Schalekamp, T., Brassé, B.P., Roijers, J.F., van Meegen, E., van der Meer, F.J., van Wijk, E.M., Egberts, A.C., de Boer, A. Clin. Pharmacol. Ther. (2007) [Pubmed]
  14. A PK-PD Model for Predicting the Impact of Age, CYP2C9, and VKORC1 Genotype on Individualization of Warfarin Therapy. Hamberg, A.K., Dahl, M.L., Barban, M., Scordo, M.G., Wadelius, M., Pengo, V., Padrini, R., Jonsson, E.N. Clin. Pharmacol. Ther. (2007) [Pubmed]
  15. Polymorphisms in Vitamin K-Dependent gamma-Carboxylation-Related Genes Influence Interindividual Variability in Plasma Protein C and Protein S Activities in the General Population. Kimura, R., Kokubo, Y., Miyashita, K., Otsubo, R., Nagatsuka, K., Otsuki, T., Sakata, T., Nagura, J., Okayama, A., Minematsu, K., Naritomi, H., Honda, S., Sato, K., Tomoike, H., Miyata, T. Int. J. Hematol. (2006) [Pubmed]
  16. VKORC1 gene variations are the major contributors of variation in warfarin dose in Japanese patients. Obayashi, K., Nakamura, K., Kawana, J., Ogata, H., Hanada, K., Kurabayashi, M., Hasegawa, A., Yamamoto, K., Horiuchi, R. Clin. Pharmacol. Ther. (2006) [Pubmed]
  17. Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin. Vecsler, M., Loebstein, R., Almog, S., Kurnik, D., Goldman, B., Halkin, H., Gak, E. Thromb. Haemost. (2006) [Pubmed]
  18. Disulfide-dependent Protein Folding Is Linked to Operation of the Vitamin K Cycle in the Endoplasmic Reticulum: A PROTEIN DISULFIDE ISOMERASE-VKORC1 REDOX ENZYME COMPLEX APPEARS TO BE RESPONSIBLE FOR VITAMIN K1 2,3-EPOXIDE REDUCTION. Wajih, N., Hutson, S.M., Wallin, R. J. Biol. Chem. (2007) [Pubmed]
  19. Compound heterozygosity of novel missense mutations in the gamma-glutamyl-carboxylase gene causes hereditary combined vitamin K-dependent coagulation factor deficiency. Darghouth, D., Hallgren, K.W., Shtofman, R.L., Mrad, A., Gharbi, Y., Maherzi, A., Kastally, R., LeRicousse, S., Berkner, K.L., Rosa, J.P. Blood (2006) [Pubmed]
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