Vitamin K Epoxide Reductase Complex, Subunit 1 Protéines (VKORC1)

Human Vitamin K Epoxide Reductase Complex, Subunit 1 (VKORC1) interaction partners

1. The presence of VKORC1 (rs9923231 and rs9934438) allelic variants in the family members suffering from idiopathic pulmonary fibrosis (IPF) indicate a previously unsuspected link between these variants and IPF.

2. VKROC1 was significantly down-regulated in hepatic tumors and showed prolonged activated partial prothrombin time (APTT). In vivo investigations further showed that VKORC1 expression was promoted by p-mTOR and repressed by p-ERK in both hepatoma and hepatocytes.

3. VKORC1 rs9923231 determines warfarin dose for Han Chinese atrial fibrillation patients undergoing catheter ablation.

4. The multivariate regression model was produced, R(2) = 0.05% for age (p = 0.04), R(2) = 6% for VKORC1 (p = 0.03), the model for estimating warfarin dose R(2) = 17% (p > 0.05).

5. These preliminary results strongly support the use of VKORC1 (-1639G>A) rs9923231 polymorphism for genetically guided initial warfarin dosing in South Indian patients with heart valve replacements.

6. individuals with polymorphism of CYP2C9 and VKORC1, either alone or combined, are more susceptible to experience bleeding episodes as adverse effect in comparison to individuals having no polymorphism. Similarly, patients having wild (*1/*1) CYP2C9 or VKORC1 GG haplotype may need higher dose of warfarin to maintain INR in therapeutic range.

7. we have established KO HEK 293T cell lines that express either endogenously VKORC1 or VKORC1L1, and found that VKORC1 is more sensitive to OACs than VKORC1L1, whereas rodenticides apparently inhibit both VKOR enzymes equally

8. the VKORC1 -1639G>A polymorphism is not a risk factor for postmenopausal osteoporosis

9. In this study, we showed that patients with VKORC1-1639GA and CYP2C9*1/*1 alleles have lower sensitivity for warfarin than those with VKORC1-1639AA and CYP2C9*1/*1 alleles.

10. VKORC1-1639A variant allele influenced warfarin daily maintenance dosage among our small, likely admixed Black patient population.

11. Polymorphism in the promoter region of VKORC1 is effective in warfarin medication.

12. The plasma S-warfarin (Cp(S)) time courses following the genotype-based dosing algorithms simulated using the PPK estimates showed African Americans with CYP2C9*1/*1 and any of the VKORC1 genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than in Asians and whites.

13. The final regression models for White and Black patients (Fig. 1) included age, weight, prosthetic valves, amiodarone use, CYP2C9*3, and VKORC1 3673 G>A genotypes as covariates, whereas possession of CYP2C9*2 and simvastatin use were retained in the final model for White, but not Black patients.

14. No relationship between VKORC1 variants and clinical outcomes in elderly patients treated with vitamin K antagonists.

15. Until the age of 19, weight has a far greater effect on Vitamin K antagonist dosing variation than VKORC1 and CYP2C9 polymorphisms. During the age of 20-40years, VKORC1 and CYP2C9 polymorphisms play a significant role.

16. The VKORC1: c.-1639 G>A polymorphism is associated with aneurysms of the ascending aorta.

17. 1639G4A polymorphism of the vitamin K epoxide reductase complex subunit 1 gene (VKORC1) is likely to be a new risk factor of Retinal Vascular Occlusion.

18. Studied the association of CYP2C9*2 (430C/T), *3 (1075A/C) and VKORC1 (-1639G/A) polymorphisms on warfarin dose requirements in patients post cardiac valve surgery. Found age and presence of CYP2C9 *2 allele significantly affect the daily dosage of warfarin during initiation of warfarin therapy after cardiac valve replacement surgery.

19. The expression of VKOR in benign prostate epithelial cells, along with the association between a functional VKOR SNP and prostate cancer risk, suggests a possible role for VKOR in mediating the effect of warfarin on prostate cancer risk.

20. analysis of VKORC1 AA-CYP2C9*1*1 genotypes reveals dosing algorithms for vitamin K antagonists

Mouse (Murine) Vitamin K Epoxide Reductase Complex, Subunit 1 (VKORC1) interaction partners

1. quantified mRNA levels for VKORC1, VKORC1L1, GGCX, and NQO1 and measured VKOR enzymatic activities in 29 different tissues

2. OCN is gamma-carboxylated by the gamma-carboxylase (GGCX) on three glutamic acid residues, a cellular process requiring reduction of vitamin K by a second enzyme, VKORC1.

3. The involvement of VKORC1L1 in VKOR activity partly explains the low susceptibility of some extrahepatic tissues to vitamin K antagonists.

4. The three most frequently found sequence variants are associated with a substantial loss of rodenticide efficacy of first-generation anticoagulants, as well as the second-generation compound bromadiolone and most probably also difenacoum.

5. role in vitamin K-dependent gamma-glutamyl carboxylation; the knockout mice die within 20 days after birth due to intracerebral haemorrhage

6. molecular cloning [VKORC1]

7. The genetic basis for resistance to anticoagulants lies in mutations in Vkorc1.

8. An analysis of novel mutations show that the VKORC1 gene is the main target for spontaneous mutations conferring warfarin resistance.

9. Each VKORC1 T-allele present in patients from the Rotterdam anticoagulation therapy study is shown to decrease the required acenocoumarol dosage by 5.1 mg/week.