GenesPolymorphismsPolymorphismCYP2C9 and VKORC1GenotypeGenotypesReductase complexSubunitEnzymeVariantsVKORMutationsRecyclesAnticoagulantCoumarinRegeneration of vitaminCarboxylationAntagonistConcomitantGgcxHemostasisSignificantlyCytochromePreventsOral anticoagulantsPredictInfluenceComplexSynthesisOsteocalcinLiverBloodVariationsTherapeuticPatientsTarget
Genes13
- Certain common changes (polymorphisms) in the CYP2C9 and VKORC1 genes account for most of the variation in warfarin metabolism due to genetic factors. (medlineplus.gov)
- While changes in specific genes, particularly CYP2C9 and VKORC1 , affect how the body reacts to warfarin, many other factors, including sex, age, weight, diet, and other medications, also play a role in the body's interaction with this drug. (medlineplus.gov)
- From results of clinical studies, genetic variation in the CYP2C9 and/or VKORC1 genes can, in concert with clinical factors, predict how each individual responds to warfarin. (cms.gov)
- This genetic analysis detects variations across four genes ( VKORC1 , CYP2C9 , GGCX and CYP4F2 ), which explain a large proportion of warfarin dose variation. (ancienthaplogroups.com)
- The VKORC1, CYP2C9, GGCX and CYP4F2 genes are all located on autosomal chromosomes and we each inherit two copies of all the genes on the autosomal chromosomes. (ancienthaplogroups.com)
- This means that we can inherit several different combinations of the VKORC1, CYP2C9, GGCX and CYP4F2 genes and each combination affects the required warfarin dosage. (ancienthaplogroups.com)
- A simple DNA test can be completed to find out which versions of VKORC1, CYP2C9, GGCX and CYP4F2 genes were inherited. (ancienthaplogroups.com)
- Pharmacodynamic properties are affected due to variations in genes that affect drug targets, for example the VKORC1 gene which codes for active sites of the enzyme, epoxide reductase. (panaceapharmaprojects.com)
- SNPs in the additional genes of the vitamin K cycle concomitant medication nicotine use and alcohol usage did not forecast phenprocoumon concentrations and phenprocoumon dose requirements inside a multiple linear regression model. (liveconscience.com)
- Growing evidence indicates that up to 60% of the individual pharmacological response to coumarins might be due to genetic variables and affected by polymorphisms in the genes encoding two enzymes, namely, vitamin K epoxide reductase (VKOR) and cytochrome P450 CYP2C9. (edu.au)
- Nearly 30 genes have been reported in association with warfarin pharmacogenetics but genetic polymorphisms in the genes encoding CYP2C9 and VKORC1 have been shown to act as the most important determinants of drug dosage requirements. (comu.edu.tr)
- Research in the RECAVA network has discovered that two acquired factors (age and body mass index ) and three genetic polymorphisms ( genes VKORC1, CYP2C9 and CYP4F2) are useful to establish the correct dosage . (wikidoc.org)
- Influence of polymorphisms in CYP2C9, VKORC1, MDR1 and APOE genes on the warfarin maintenance dose in Brazilian patients. (cdc.gov)
Polymorphisms6
- Aim In the present study, correlation between specific XbaI and PvuII polymorphisms in the ERα gene and selected polymorphisms in the VKORC1 gene with low BMD and fractures risk were investigated in 345 postmenopausal Palestinian women including 165 osteoporotic, 93 osteopenic and 86 normal subjects using allele-specific polymerase chain reaction (PCR) and RFLP-PCR technology. (qscience.com)
- Conclusions These findings indicate that specific polymorphisms in the ERα gene and VKORC1 gene are correlated with variation in BMD levels among our subjects. (qscience.com)
- Certain VKORC1 gene polymorphisms decrease the amount of functional VKORC1 enzyme available to help activate clotting proteins. (medlineplus.gov)
- DNA sensors to assess the effect of VKORC1 and CYP2C9 gene polymorphisms on warfarin dose requirement in Chinese patients with atrial fibrillation. (cdc.gov)
- The emphasis placed hitherto on CYP2C9 and VKORC1 polymorphisms is also questioned by recent studies implicating a novel polymorphism in the CYP4F2 gene, especially its variant V433M allele that also influences variability in warfarin dose requirement. (rockinhibitor.com)
- Although it might be premature to recommend routine genetic testing, the future development and clinical validation of simple but comprehensive algorithms integrating the most informative gene polymorphisms (VKORC1 and CYP2C9) with some demographic information (age, race, body mass index) and clinical variables (comorbidities, drugs interference), and standardized dietary intake of vitamin K may provide a valuable tool in the care of patients on OAT with conventional VKAs. (edu.au)
Polymorphism9
- No clear link between VKORC1 genetic polymorphism and the risk of venous thrombosis or peripheral arterial disease. (123dok.net)
- High prevalence of VKORC1*3 (G9041A) genetic polymorphism in north Indians: A study on patients with cardiac disorders on acenocoumarol. (cdc.gov)
- Vitamin K-epoxide reductase 1 (VKORC1) G-1639A gene polymorphism is known to affect an enzyme activity and bioavailability of vitamin K. To date, there is a little data on the role of VKORC1 G-1639A variation in venous thromboembolism (VTE) development, in particular, in patients with inherited thrombophilia. (isth.org)
- To assess effect of the VKORC1 G-1639A gene polymorphism on the risk of VTE development in patients from North-Western Russia. (isth.org)
- Warfarin, an inhibitor of epoxide reductase, has a reduced efficacy in individuals with a genetic polymorphism of the VKORC1 gene. (panaceapharmaprojects.com)
- As a result of this polymorphism, more vitamin K will be activated that requires a higher dose of warfarin to be inhibited. (panaceapharmaprojects.com)
- This really is followed by details on polymorphism of vitamin K epoxide reductase in addition to a note that about 55 with the variability in warfarin dose might be explained by a combination of MedChemExpress VRT-831509 VKORC1 and CYP2C9 genotypes, age, height, body weight, interacting drugs, and indication for warfarin therapy. (rockinhibitor.com)
- Polymorphism of VKORC1 has been shown to become of higher significance than CYP2C9 polymorphism. (rockinhibitor.com)
- Whereas CYP2C9 genotype accounts for 12?8 , VKORC1 polymorphism accounts for about 25?0 of your inter-individual variation in warfarin dose [25?7].Nevertheless,prospective proof for any clinically relevant benefit of CYP2C9 and/or VKORC1 genotype-based dosing is still very limited. (rockinhibitor.com)
CYP2C9 and VKORC15
- Warfarin dose requirements with different genotypes of CYP2C9 and VKORC1 for patients with atrial fibrillation and valve replacement. (cdc.gov)
- Clinical application of a new warfarin-dosing regimen based on the CYP2C9 and VKORC1 genotypes in atrial fibrillation patients. (cdc.gov)
- There was no specific guidance on dose by genotype combinations, and healthcare specialists are certainly not necessary to conduct CYP2C9 and VKORC1 testing before initiating warfarin therapy. (rockinhibitor.com)
- Many retrospective studies have certainly reported a strong association involving the presence of CYP2C9 and VKORC1 variants as well as a low warfarin dose requirement. (rockinhibitor.com)
- Beneath the situations, genotype-based customized therapy, with the promise of appropriate drug in the suitable dose the first time, is definitely an exaggeration of what dar.12324 is achievable and substantially much less appealing if genotyping for two apparently important markers referred to in drug labels (CYP2C9 and VKORC1) can account for only 37?8 with the dose variability. (rockinhibitor.com)
Genotype10
- The bottom line of this report is that those with the "resistant" genotype (GG) who typically require a higher dose of warfarin show the greatest fall in the INR (or require the largest upward dose adjustment of warfarin) when daily vitamin K supplementation (150 mcg) is initiated to help stabilize the INR. (clotcare.com)
- On the other hand, those who are more sensitive to warfarin (GA and AA genotype), show less of a change - or no change - in the INR with daily vitamin K supplementation. (clotcare.com)
- It appears that the exact opposite may be the case since those with the GG genotype apparently have a form of VKORC1 that is better able to regenerate vitamin K hydroquinone (required for carboxylation of the clotting factors) from the vitamin K 2,3-epoxide. (clotcare.com)
- Whether genotype influenced the impact of vitamin K supplementation on INR stability was not examined in this report. (clotcare.com)
- Both the CYP2C9 genotype and VKORC1 haplotype had a significant influence on the required warfarin dose after the first 2 weeks of therapy. (nih.gov)
- Lack of Association of Clinical Factors (SAMe-TT2R2) with CYP2C9/VKORC1 Genotype and Anticoagulation Control Quality. (cdc.gov)
- In the group of patients without FII and FV gene mutations, the frequency of the VKORC1 -1639AA genotype was almost equal to that in CG (17.1% vs. 16.5%, respectively). (isth.org)
- We suggest that VKORC1 -1639AA genotype could have protective effect on VTE development in patients with FII G20210A mutation from North-Western Russia. (isth.org)
- Kapustin S, Chechulova A, Svitina S, Sidorova J, Burakov V, Soroka V, Soldatenkov V, Papayan L. VKORC1 -1639AA Genotype Is a Possible Protective Factor for Venous Thromboembolism Development in Patients with FII G20210A Mutation from North-Western Russia [abstract]. (isth.org)
- Dosing Recommendations with Consideration of Genotype : Genetic variations in the CYP450 2C9 and vitamin K epoxide reductase complex 1 (VKORC1) enzymes can significantly influence patient response to this drug as indicated by the prothrombin time (PT)/INR. (web.app)
Genotypes2
- In 297 patients starting warfarin therapy, we assessed CYP2C9 genotypes (CYP2C9 *1, *2, and *3), VKORC1 haplotypes (designated A and non-A), clinical characteristics, response to therapy (as determined by the international normalized ratio [INR]), and bleeding events. (nih.gov)
- Determination of Pleiotropic Effect of Warfarin in VKORC1 and CYP2C9 Genotypes in Patients With Heart Valve Replacement. (cdc.gov)
Reductase complex3
- The reduction of vitamin K to vitamin K hydrochinon depends on the vitamin K epoxide reductase complex subunit 1 (VKORC1). (qscience.com)
- The vitamin K-epoxide reductase complex (VKOR) allows vit-amin K epoxide to be converted back into reduced vitvit-amin K. Its activity is the rate-limiting step of vitamin K-dependent protein gamma-carboxylation. (123dok.net)
- Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase. (smpdb.ca)
Subunit2
- Warfarin affects the vitamin K-dependent clotting factors II, VII, IX, and X. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide. (cms.gov)
- It elicits an anticoagulant effect by interfering with the synthesis of vitamin K-dependent clotting factors in the liver via inhibition of the vitamin K epoxies reeducates complex subunit 1 (VKORC1) [2]. (austinpublishinggroup.com)
Enzyme9
- Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses, but the role of these variants during initial anticoagulation is not clear. (nih.gov)
- The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme. (medlineplus.gov)
- The VKORC1 enzyme helps turn on (activate) clotting proteins in the pathway that forms blood clots . (medlineplus.gov)
- Warfarin prevents (inhibits) the action of the VKORC1 enzyme and slows the activation of clotting proteins and clot formation. (medlineplus.gov)
- Individuals develop warfarin sensitivity because a lower warfarin dose is needed to inhibit the VKORC1 enzyme, as there is less functional enzyme that needs to be suppressed. (medlineplus.gov)
- Genetic variants in the warfarin target, the vitamin K epoxide reductase (VKORC1), as well as the warfarin metabolizing enzyme, cytochrome P450 2C9 (CYP2C9), influence the variation in patient response. (medicineworks.com)
- The VKORC1 enzyme recycles inactive vitamin K1 after it has helped to activate several proteins involved in clotting. (ancienthaplogroups.com)
- This enzyme is responsible for activating vitamin K and coagulation factors. (panaceapharmaprojects.com)
- Wajih N, Hutson SM, Owen J, Wallin R: Increased production of functional recombinant human clotting factor IX by baby hamster kidney cells engineered to overexpress VKORC1, the vitamin K 2,3-epoxide-reducing enzyme of the vitamin K cycle. (idhinhibitor.com)
Variants3
- Genetically mutated variants of the gene have been shown to cause warfarin-resistance phenotypes as well as pathogenic deficiency of all vitamin K-dependent coagulation factors. (eur.nl)
- Distribution of the VKORC1 G-1639A gene variants was similar in both VTE patients and controls. (isth.org)
- VKORC1 and CYP2C9 variants, together with physical factors, are responsible for about 55% of the variability in optimal coumarin dosage. (viennalab.com)
VKOR4
- Vertebrates possess 2 proteins with vitamin K oxidoreductase (VKOR) activity: VKORC1, whose vitamin K reduction supports vitamin K-dependent (VKD) protein carboxylation, and VKORC1-like 1 (VKORC1L1), whose function is unknown. (jci.org)
- VKORC1 expression and VKOR activity increased during late embryogenesis and following birth, while VKORC1L1 expression was unchanged. (jci.org)
- 99%) VKOR activity was due to VKORC1. (jci.org)
- Warfarin inhibits vitamin K epoxide reductase (VKOR). (comu.edu.tr)
Mutations1
- Watzka M, Geisen C, Bevans CG, Sittinger K, Spohn G, Rost S, Seifried E, Muller CR, Oldenburg J: Thirteen novel VKORC1 mutations associated with oral anticoagulant resistance: insights into improved patient diagnosis and treatment. (pathbank.org)
Recycles1
- Recycles vitamin K epoxide to the reduced form of vitamin K, an essential cofactor in formation of active clotting factors II, VII, IX and X via gamma-glutamyl carboxylation. (standardofcare.com)
Anticoagulant2
- Vitamin K plays a crucial role in hemostasis by activating both procoagulant (FII, VII, IX, X) and anticoagulant (proteins C, S, Z) factors. (isth.org)
- Acenocoumarol is an anticoagulant that functions as a vitamin K antagonist (like warfarin ). (wikidoc.org)
Coumarin3
- Coumarin inhibits the recycling of vitamin K, an essential co-factor for blood clotting proteins, by blocking VKORC1. (viennalab.com)
- To improve safety and efficacy of coumarin (e.g. warfarin) treatment, genetic testing of VKORC1 and CYP2C9 was recommended by the FDA prior to therapy initiation. (viennalab.com)
- c.-1639G>A affecting VKORC1 gene expression has been shown MGC116786 to be a major determinant of coumarin dose variability accounting for 13-49% of dose response [7-9]. (liveconscience.com)
Regeneration of vitamin1
- By inhibiting vitamin K epoxide reductase complicated 1 (VKORC1), S-warfarin prevents regeneration of vitamin K hydroquinone for activation of vitamin K-dependent clotting elements. (rockinhibitor.com)
Carboxylation4
- Vitamin K, discovered in the 1930s, functions as a cofactor for the posttranslational carboxylation of glutamate residues (1). (123dok.net)
- We found that Vkorc1-/-;Vkorc1l1-/- mice died at birth with severe hemorrhaging, indicating that VKORC1L1 supports carboxylation during the pre- and perinatal periods. (jci.org)
- VKORC1L1 levels in Vkorc1-/- mouse liver may therefore be insufficient for supporting carboxylation beyond day 7. (jci.org)
- In support of this conclusion, VKORC1L1 overexpression in liver rescued carboxylation and hemostasis in adult Vkorc1-/- mice. (jci.org)
Antagonist1
- Vitamin-K-antagonist phenprocoumon versus low-dose direct oral anticoagulants (DOACs) in patients with atrial fibrillation: a real-world analysis of German claims data. (cdc.gov)
Concomitant1
- Genetic factors including VKORC1: concomitant drugs/diet: and various disease states can impact on the efficacy of warfarin by changing its pharmacokinetics. (austinpublishinggroup.com)
Ggcx2
- VKD proteins include liver-derived coagulation factors, and hemorrhaging and lethality were previously observed in mice lacking either VKORC1 or the γ-glutamyl carboxylase (GGCX) that modifies VKD proteins. (jci.org)
- Vkorc1-/- mice survived longer (1 week) than Ggcx-/- mice (midembryogenesis or birth), and we assessed whether VKORC1L1 could account for this difference. (jci.org)
Hemostasis1
- Additional studies showed that only VKORC1 sustains hemostasis beyond P7. (jci.org)
Significantly3
- The warfarin doses before vitamin K were not significantly different between the 3 groups and, in fact, the absolute mean dose was lower in the GG group than in the GA or the AA group (3.23 mg, 4.52 mg, and 3.50 mg, respectively). (clotcare.com)
- The warfarin doses after the addition of vitamin K also were not significantly different (mean daily doses of 4.05 mg, 4.86 mg, and 3.50 mg for GG, GA, and AA, respectively) - and the mean dose for the "resistant" group remained lower than the mean dose for the "average" (GA) group. (clotcare.com)
- region of the VKORC1 gene (9041 AG and GG) was significantly associated with low BMD. (qscience.com)
Cytochrome1
- cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) . (ssht.sk)
Prevents1
- Warfarin prevents this vitamin K1 recycling, thereby depleting active vitamin K1. (ancienthaplogroups.com)
Oral anticoagulants1
- and details of non-vitamin K oral anticoagulants, such as factor Xa inhibitors, rivaroxaban, apixaban, edoxaban, and the factor IIa inhibitor dabigatran are all included in this section. (medthority.com)
Predict2
- Pharmacogenomic testing of CYP2C9 or VKORC1 alleles to predict a patient's response to warfarin occurs ideally prior to initiation of the drug. (cms.gov)
- Prospectively, in Medicare-aged subjects whose warfarin therapy management includes pharmacogenomic testing of CYP2C9 or VKORC1 alleles to predict warfarin response, what is the frequency and severity of the following outcomes, compared to subjects whose warfarin therapy management does not include pharmacogenomic testing? (cms.gov)
Influence1
- Although a variety of other factors may influence the response to vitamin K supplementation, the mean increase in warfarin dose that was required was 25% for resistant (GG) patients, 8% for GA patients, and 0% for sensitive AA patients following the implementation of daily vitamin K supplementation. (clotcare.com)
Complex1
- After another three decades, in 2004, the complex biochemical relationship between vitamin K, its epoxide, and coumarins was enlightened by identifying the VKORC1 gene. (eur.nl)
Synthesis1
- For the discovery of vitamin K and the purification, characterization and synthesis of the vitamin, Dam and Doisy were awarded the Nobel Prize in Medicine in 1943. (eur.nl)
Osteocalcin1
- Matrix Gla protein and bone Gla protein (osteocalcin), two vitamin K-dependent proteins involved in calcium home-ostasis, have been implicated in the pathogenesis of athero-sclerosis, myocardial infarction and stroke (2, 3). (123dok.net)
Liver1
- Phenindione works by thinning the blood, which is done through the antagonization of vitamin K. This antagonization is needed to create the factors that cause clotting in the liver. (pathbank.org)
Blood1
- Warfarin decreases blood coagulation by inhibiting the vitamin K epoxide reductase, encoded by the VKORC1 gene. (ancienthaplogroups.com)
Variations1
- Genotyping for the VKORC1 G-1639A, FII G20210A and FV G1691A variations was performed by PCR-RFLP. (isth.org)
Therapeutic1
- As compared with patients with the non-A/non-A haplotype, patients with the A/A haplotype of VKORC1 had a decreased time to the first INR within the therapeutic range (P=0.02) and to the first INR of more than 4 (P=0.003). (nih.gov)
Patients1
- Therefore, the warfarin-resistant "GG patients" can better utilize - or regenerate - whatever vitamin K is available while the more warfarin sensitive "AA patients" apparently can not "utilize" the additional vitamin K as well. (clotcare.com)
Target1
- Initial variability in the INR response to warfarin was more strongly associated with genetic variability in the pharmacologic target of warfarin, VKORC1, than with CYP2C9. (nih.gov)