Редактирование: VKORC1

Vitamin K epoxide reductase complex subunit 1 (EC 1.17.4.4) (Vitamin K1 2,3-epoxide reductase subunit 1) [VKOR] [MSTP134] [MSTP576] [UNQ308/PRO351]

==Publications==

{{medline-entry
|title=The effect of [[CYP2C9]], [[VKORC1]] genotypes and old age on warfarin pharmacologic sensitivity in korean patients with thromboembolic disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22075505
|abstract=The therapeutic dose of warfarin is dependent upon intrinsic patient characteristics that are highly variable. We assessed the effects of [[CYP2C9]], [[VKORC1]] 1173 C/T polymorphisms, and old age on warfarin dosing and sensitivity by measuring plasma S-/R-warfarin levels in Korean patients. INR and the plasma S-/R-warfarin concentrations were determined in 58 patients who had the [[VKORC1]] 1173C/T [[CYP2C9]] genotypes, were on a long-term anticoagulation regimen with warfarin, and took a daily dose of warfarin. The pharmacokinetic sensitivity of warfarin was significantly higher in the [[CYP2C9]] *1/*3 genotypes than in the [[CYP2C9]] *1/*1 genotypes [ratio of S-warfarin concentration/dose, 0.53 vs. 0.21; p=0.01]. Pharmacodynamic sensitivity in older patients (≥ 75 years) with the [[CYP2C9]] *1/*1 and [[VKORC1]] 1173 TT genotypes was significantly higher as compared to younger patients (<75 years) [Ratio of INR/S-warfarin concentration, 4.88 vs. 3.41; p = 0.026]. The [[CYP2C9]]*3 allele and old age (≥ 75 years) with the [[VKORC1]] 1173 T allele were also associated with increased risk of over-anticoagulation. The increase of over-anticoagulation risk and warfarin sensitivity is related to the [[CYP2C9]]*3 allele and old age with the [[VKORC1]] 1173 T allele in Korean patients with thromboembolic disease. These findings suggest that a lower initial and maintenance dose should be considered for the patients with [[CYP2C9]] *3 allele and advanced age in this patient population. However, due to the limited number of patients in the study population, our finding needs to be confirmed by a larger, well-controlled study.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Anticoagulants
* Aryl Hydrocarbon Hydroxylases
* Asian Continental Ancestry Group
* Blood Coagulation
* Cytochrome P-450 CYP2C9
* Dose-Response Relationship, Drug
* Female
* Humans
* Korea
* Male
* Middle Aged
* Mixed Function Oxygenases
* Thromboembolism
* Treatment Outcome
* Vitamin K Epoxide Reductases
* Warfarin


}}
{{medline-entry
|title=Contribution of age, body weight, and [[CYP2C9]] and [[VKORC1]] genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17899045
|abstract=The objective of this study was to assess the contribution of the [[VKORC1]] and [[CYP2C9]] genotypes and age, body size, and weight of the patients to the warfarin dose requirement in a Chinese population. Blood samples were collected from 178 Chinese patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the target range (1.5-3.0). The polymorphisms for the [[VKORC1]] (-1639GA) and [[CYP2C9]]*3 genotypes, venous INR, and plasma concentration and unbound concentration of warfarin were then analyzed. [[VKORC1]] (-1639G>A) genotyping showed that 149 patients were homozygous AA, 28 were heterozygous GA, and one was homozygous for the GG genotype. [[CYP2C9]]*3 genotyping showed that 162 patients were *1/*1, and 16 patients were heterozygous *1/*3. Patients with the [[VKORC1]](-1639 GG GA) (3.32  /- 1.02 mg/day) and [[CYP2C9]]*1/*1 (2.06  /- 0.82 mg/day) genotypes required a significantly higher warfarin dose than those with the -1639 AA (1.76  /- 0.57 mg/day; P < 0.001) or [[CYP2C9]]*1/*3 (1.60  /- 1.29 mg/day; P < 0.001), genotype. The multiple linear regression model for warfarin dose indicated significant contributions from age (r (2) = 0.084; P < 0.001), weight (r (2) = 0.063; P < 0.001), [[VKORC1]] genotype (r (2) = 0.494; P < 0.001), and age, weight, and [[CYP2C9]] and [[VKORC1]] genotype together (r (2) = 0.628; P < 0.001). This study shows that age, weight and the [[VKORC1]] and [[CYP2C9]] polymorphism affect warfarin dose requirements in our sample of Chinese patients receiving long-term therapy and showing stable control of anticoagulation. It is anticipated that the use of dosing regimens modified by taking into account the contribution of age, weight, and the [[CYP2C9]] and [[VKORC1]] genotypes has the potential to improve the safety of warfarin therapy.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Anticoagulants
* Aryl Hydrocarbon Hydroxylases
* Blood Coagulation
* Body Weight
* China
* Cytochrome P-450 CYP2C9
* Female
* Genotype
* Humans
* International Normalized Ratio
* Male
* Middle Aged
* Mixed Function Oxygenases
* Pharmacogenetics
* Polymorphism, Genetic
* Vitamin K Epoxide Reductases
* Warfarin

|full-text-url=https://sci-hub.do/10.1007/s00228-007-0381-6
}}
{{medline-entry
|title=A PK-PD model for predicting the impact of age, [[CYP2C9]], and [[VKORC1]] genotype on individualization of warfarin therapy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17301738
|abstract=The aim of this study was to characterize the relationship between warfarin concentrations and international normalized ratio (INR) response and to identify predictors important for dose individualization. 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. The anticoagulant response was best described by an inhibitory E(MAX) model, with S-warfarin concentration as the only exposure predictor for response. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. [[CYP2C9]] genotype and age were identified as predictors for S-warfarin clearance, and [[VKORC1]] genotype as a predictor for warfarin sensitivity. Predicted INR curves indicate important steady-state differences between patients with different sets of covariates; differences that cannot be foreseen from early INR assessments alone. It is important to account for [[CYP2C9]] and [[VKORC1]] genotypes and age to improve a priori and a posteriori individualization of warfarin therapy.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Algorithms
* Anticoagulants
* Aryl Hydrocarbon Hydroxylases
* Cytochrome P-450 CYP2C9
* DNA
* Databases, Factual
* Female
* Genotype
* Humans
* Male
* Middle Aged
* Mixed Function Oxygenases
* Models, Statistical
* Pharmacokinetics
* Population
* Stereoisomerism
* Vitamin K Epoxide Reductases
* Warfarin

|full-text-url=https://sci-hub.do/10.1038/sj.clpt.6100084
}}