更新于：2024-11-01

VKOR x NQO1

更新于：2024-11-01

基本信息

关联

项与 VKOR x NQO1 相关的药物

Acenocoumarol

醋硝香豆素

靶点

NQO1 x VKOR

作用机制

NQO1抑制剂 [+2]

在研机构-

原研机构-

在研适应症

血栓栓塞

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区-

首次获批日期1800-01-20

项与 VKOR x NQO1 相关的临床试验

NCT03153150 / Completed临床3期IIT

Start or STop Anticoagulants Randomised Trial (SoSTART) After Spontaneous Intracranial Haemorrhage

Primary research question: For adults surviving spontaneous (non-traumatic) symptomatic intracranial haemorrhage with persistent/paroxysmal atrial fibrillation/flutter (AF), does starting full treatment dose oral anticoagulation (OAC) result in a beneficial net reduction of all serious vascular events compared with not starting OAC?
Trial design: Investigator-led, multicentre, randomised, open, assessor-masked, parallel group, clinical trial of investigational medicinal product (CTIMP) prescribing strategies. Investigators plan for a pilot phase, followed by a safety phase.

开始日期2018-03-28

申办/合作机构

The University of Edinburgh

[+1]

100 项与 VKOR x NQO1 相关的临床结果

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100 项与 VKOR x NQO1 相关的转化医学

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0 项与 VKOR x NQO1 相关的专利（医药）

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项与 VKOR x NQO1 相关的文献（医药）

2023-06-01·Clinical pharmacokinetics

Genetic Factors Influencing Warfarin Dose in Han Chinese Population: A Systematic Review and Meta-Analysis of Cohort Studies.

Review

作者: Wang, Xiang ; Jin, Pengfei ; Zhao, Ming ; Zhang, Yatong ; Tian, Chao ; Zhao, Zinan ; Liu, Deping ; Hu, Xin ; Dong, Shujie ; Zhao, Fei ; Liu, Junpeng

OBJECTIVETo investigate the association of single nucleotide polymorphisms (SNPs) of various genes known to influence mean daily warfarin dose (MDWD) in the Han Chinese population.METHODSThe study is a systematic review and meta-analysis. Selected studies retrieved by searching Pubmed, Embase (Ovid), Medline, CNKI, Wanfang data, and SinoMed (from their inception to 31 August 2022) for the cohort studies assessing genetic variations that may possibly influence MDWD in Chinese patients were included.RESULTA total of 46 studies including a total of 10,102 Han Chinese adult patients were finally included in the meta-analysis. The impact of 20 single nucleotide polymorphisms (SNPs) in 8 genes on MDWD was analyzed. The significant impact of some of these SNPs on MDWD requirements was demonstrated. Patients with CYP4F2 rs2108622 TT, EPHX1 rs2260863 GC, or NQO1 rs1800566 TT genotype required more than 10% higher MDWD. Furthermore, patients with ABCB1 rs2032582 GT or GG, or CALU rs2290228 TT genotype required more than 10% lower MDWD. Subgroup analysis showed that patients with EPHX1 rs2260863 GC genotype required 7% lower MDWD after heart valve replacement (HVR).CONCLUSIONThis is the first systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) of various genes known to influence MDWD besides CYP2C9 and VKORC1 in the Han Chinese population. CYP4F2 (rs2108622), GGCX (rs12714145), EPHX1 (rs2292566 and rs2260863), ABCB1 (rs2032582), NQO1 (rs1800566), and CALU (rs2290228) SNPs might be moderate factors affecting MDWD requirements.REGISTERED INFORMATIONPROSPERO International Prospective Register of Systematic Reviews (CRD42022355130).

2021-01-01·Clinical and Translational Science3区 · 医学

Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos

3区 · 医学

ArticleOA

作者: Scott, Stuart A. ; Botton, Marianna R. ; Camargo Tavares, Letícia ; Kaye, Justin ; Duconge, Jorge ; Steiner, Heidi ; Claudio, Karla ; Caleb Junior de Lima Santos, Paulo ; Rodrigues Marcatto, Leiliane ; El Rouby, Nihal ; Karnes, Jason ; Cavallari, Larisa H. ; Lubitz, Steve A. ; Fallon, Echo N. ; Yee, Kevin

We conducted a multi‐site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from four institutions in the United States (n = 411) and Brazil (n = 663) were genotyped for VKORC1 c.‐1639G> A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test the association between warfarin dose and genotype, adjusting for clinical factors, with further testing in an independent cohort of Brazilians. In the U.S. cohort, VKORC1 and CYP2C9 variants were associated with lower warfarin dose (β = −0.29, P < 2.0 × 10−16; β = −0.21, P = 4.7 × 10−7, respectively) whereas CYP4F2 and NQO1 variants were associated with higher dose (β = 0.10, P = 2 × 10−4; β = 0.10, P = 0.01, respectively). Associations with VKORC1 (β = −0.14, P = 2.0 × 10−16), CYP2C9 (β = −0.07, P = 5.6 × 10−10), and CYP4F2 (β = 0.03, P = 3 × 10−3), but not NQO1*2 (β = 0.01, P = 0.30), were replicated in the Brazilians, explaining 43–46% of warfarin dose variability among the cohorts from the U.S. and Brazil, respectively. We identified genetic associations with warfarin dose requirements in the largest cohort of ancestrally diverse, warfarin‐treated Latinos from the United States and Brazil to date. We confirmed the association of variants in VKORC1, CYP2C9, and CYP4F2 with warfarin dose in Latinos from the United States and Brazil.

2020-01-01·Pharmacogenomics4区 · 医学

Impact of CYP2C9 , VKORC1 , ApoE and ABCB1 Polymorphisms on Stable Warfarin Dose Requirements in Elderly Chinese Patients

4区 · 医学

Article

作者: Dong, Jing ; Lai, Xiaoyin ; Li, Wenyan ; Shi, Guohua ; Chen, Liwen ; Zhao, Ping ; Li, Longxuan

Aim: To analyze the impact of nongenetic factors and gene polymorphisms on warfarin dose requirements in elderly Shanghai Han Chinese patients. Materials & methods: Genotypes of CYP2C9 (rs1799853 and rs1057910), FPGS (rs7856096), ApoE (rs7412 and rs429358), GGCX (rs699664 and rs12714145), EPHX1 (rs4653436, rs1877724, rs1051740 and rs1131873), NQO1 (rs1800566 and rs10517), ABCB1 (rs1045642), VKORC1 (rs9923231) and CYP4F2 (rs2108622) in 214 patients with stable warfarin dose were determined and their demographic characteristics were recorded. Results: Multiple linear regression analysis revealed that VKORC1 rs9923231, CYP2C9*3 rs1057910, ApoE rs7412, age, BMI and concomitant amiodarone could explain 37.0% of the individual variations of daily stable warfarin dose. Conclusion: VKORC1 rs9923231, CYP2C9*3 rs1057910, ApoE rs7412, age, BMI and concomitant amiodarone play an important role in stable dose variation of warfarin in elderly Shanghai Han Chinese patients, whereas ABCB1 rs1045642 is not a significant genetic factor.