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https://www.readbyqxmd.com/read/28079798/clinical-and-genetic-factors-associated-with-warfarin-maintenance-dose-in-northern-chinese-patients-with-mechanical-heart-valve-replacement
#1
Rui Liu, Jian Cao, Qian Zhang, Xin-Miao Shi, Xiao-Dong Pan, Ran Dong
The effects of genetic variants on warfarin dosing vary among different ethnic groups, especially in the Chinese population. The objective of this study was to recruit patients through a rigorous experimental design and to perform a comprehensive screen to identify gene polymorphisms that may influence warfarin dosing in northern Han Chinese patients with mechanical heart valve replacement. Consenting patients (n = 183) with a stable warfarin dose were included in this study. Ninety-six single nucleotide polymorphisms (SNPs) in 30 genes involved in warfarin pharmacological pathways were genotyped using the Illumina SNP GoldenGate Assay, and their associations with warfarin dosing were assessed using univariate regression analysis with post hoc comparison using least significant difference analysis...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28070807/successful-synthesis-of-active-human-coagulation-factor-vii-by-co-expression-of-mammalian-gamma-glutamyl-carboxylase-and-modification-of-vit-k-cycle-in-drosophila-schneider-s2-cells
#2
Kotomi Nagahashi, Kazuo Umemura, Naohiro Kanayama, Takayuki Iwaki
Mammalian gamma-glutamyl carboxylase and reduced vitamin K are indispensable for synthesis of mature mammalian vitamin K dependent proteins including some of blood coagulation factors (factors II, VII, IX, and X). It was well known that Drosophila melanogaster expressed gamma-glutamyl carboxylase and possessed a vit.K cycle although native substrates for them have not been identified yet. Despite the potential capability of gamma carboxylation in D. melanogaster derived cells such as S2 cells, Drosophila gamma-glutamyl carboxylase failed to gamma carboxylate a peptide fused to the human coagulation factor IX propeptide...
January 9, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28063245/dosing-algorithms-for-vitamin-k-antagonists-across-vkorc1-and-cyp2c9-genotypes
#3
Ekaterina V Baranova, Talitha I Verhoef, Georgia Ragia, Saskia Le Cessie, Folkert W Asselbergs, Anthonius de Boer, Vangelis G Manolopoulos, Anke H Maitland-van der Zee
BACKGROUND: The multicenter, single-blind, randomized EU-PACT trial compared safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep venous thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. OBJECTIVES: To explore possible reasons for the lack of differences between trial arms this secondary analysis of EU-PACT data evaluated the performance of both dosing algorithms across VKORC1-CYP2C9 genetic sub-groups...
January 7, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28049362/warfarin-dose-model-for-the-prediction-of-stable-maintenance-dose-in-indian-patients
#4
Tejasvita Gaikwad, Kanjaksha Ghosh, Peter Avery, Farhad Kamali, Shrimati Shetty
The main aim of this study was to screen various genetic and nongenetic factors that are known to alter warfarin response and to generate a model to predict stable warfarin maintenance dose for Indian patients. The study comprised of 300 warfarin-treated patients. Followed by extensive literature review, 10 single-nucleotide polymorphisms, that is, VKORC1-1639 G>A (rs9923231), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), FVII R353Q (rs6046), GGCX 12970 C>G (rs11676382), CALU c.*4A>G (rs1043550), EPHX1 c...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#5
Liuh Ling Goh, Chia Wei Lim, Wey Cheng Sim, Li Xian Toh, Khai Pang Leong
BACKGROUND: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. METHODS: We designed a 32-SNP panel for PGx testing in clinical laboratories...
2017: PloS One
https://www.readbyqxmd.com/read/28033245/vkorc1-and-cyp2c9-polymorphisms-related-to-adverse-events-in-case-control-cohort-of-anticoagulated-patients
#6
Silvia Misasi, Giuliana Martini, Oriana Paoletti, Stefano Calza, Giovanni Scovoli, Alessandra Marengoni, Sophie Testa, Luigi Caimi, Eleonora Marchina
Vitamin K antagonists (VKAs) are highly effective but have a narrow therapeutic index and require routine monitoring of the INR. The primary aim of pharmacogenetics (PGx) is to optimize patient care, achieving drug treatments that are personalized according to the genetic profile of each patient. The best-characterized genes involved in VKA PGx involve pharmacokinetics (VKORC1) and pharmacodynamics (CYP2C9) of VKA metabolism. The role of these genes in clinical outcomes (bleeding and thrombosis) during oral anticoagulant (OAC) therapy is controversial...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28032893/anticoagulation-endpoints-with-clinical-implementation-of-warfarin-pharmacogenetic-dosing-in-a-real-world-setting-a-proposal-for-a-new-pharmacogenetic-dosing-approach
#7
M J Arwood, J Deng, K Drozda, O Pugach, E A Nutescu, S Schmidt, J D Duarte, L H Cavallari
Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype-guided warfarin dosing, we aimed to examine genotype-associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced-function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7...
November 5, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28025970/impact-of-vkorc1-gene-polymorphisms-on-warfarin-maintenance-dosage-a-novel-systemic-review-and-meta-analysis-of-53-studies%C3%A2
#8
Qing-Ping Wei Tang, Feng Shi, Mei-Ling Ding, Jian Yu, Yong-Xin Hua, Yong-xin Wang
OBJECTIVE: To analyze the correlation between VKORC1 gene polymorphisms and warfarin maintenance dosage, as well as the correlation of dosage of warfarin with age and ethnicity. METHODS: We retrieved related studies published between January 2000 and March 2016 from PubMed, Embase, the Cochrane Library, Web of Science, VIP, CNKI, and Wan Fang data. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and crosscheck data...
27, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27992547/the-impact-of-genetic-and-non-genetic-factors-on-warfarin-dose-prediction-in-mena-region-a-systematic-review
#9
Loulia Akram Bader, Hazem Elewa
BACKGROUND: Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing...
2016: PloS One
https://www.readbyqxmd.com/read/27990512/warfarin-genotyping-with-hybridization-induced-aggregation-on-a-poly-ethylene-terephthalate-microdevice
#10
Hillary S Sloane, Morgan B Carter, Alexa E C Cecil, Delphine Le Roux, Daniel L Mills, James P Landers
Warfarin, a commonly prescribed oral anticoagulant, is burdened by a narrow therapeutic index and high inter-individual variability in response, making it the second leading cause of drug-related emergency room visits. Since genetic factors contribute significantly to warfarin sensitivity, a genotype-guided dosing strategy may reduce the occurrence of adverse events. While numerous methods have been demonstrated for warfarin genotyping, the specifications of most assays with respect to turnaround time and cost are not ideal for routine testing...
December 19, 2016: Analyst
https://www.readbyqxmd.com/read/27967328/a-novel-acenocoumarol-pharmacogenomic-dosing-algorithm-for-the-greek-population-of-eu-pact-trial
#11
Georgia Ragia, Vana Kolovou, Genovefa Kolovou, Stavros Konstantinides, Efstratios Maltezos, Anna Tavridou, Dimitrios Tziakas, Anke H Maitland-van der Zee, Vangelis G Manolopoulos
AIM: To generate and validate a pharmacogenomic-guided (PG) dosing algorithm for acenocoumarol in the Greek population. To compare its performance with other PG algorithms developed for the Greek population. PATIENTS & METHODS: A total of 140 Greek patients participants of the EU-PACT trial for acenocoumarol, a randomized clinical trial that prospectively compared the effect of a PG dosing algorithm with a clinical dosing algorithm on the percentage of time within INR therapeutic range, who reached acenocoumarol stable dose were included in the study...
January 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/27959270/speculations-on-vitamin-k-vkorc1-genotype-and-autism
#12
M C DeSoto
Humans vary in the gene that encodes for Vitamin K epoxide reductase complex (VKORC1). Recent research has documented the protective effect of Vitamin K on neural cells and its role in maintaining normal neural development. Of interest, specific neural effects of Vitamin K overlap with key brain development aberrations, including those associated with autism. Furthermore, Vitamin K protects against oxidative stress associated with toxic exposure. Research on the neural effects is reviewed, and a small sample of severely autistic children of Somali descent residing in the Minneapolis/St...
November 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27938396/genetic-polymorphisms-of-patients-on-stable-warfarin-maintenance-therapy-in-a-ghanaian-population
#13
William Kudzi, Samuel Yao Ahorhorlu, Bartholomew Dzudzor, Edeghonghon Olayemi, Edmund Tetteh Nartey, Richard Harry Asmah
BACKGROUND: Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR...
December 9, 2016: BMC Research Notes
https://www.readbyqxmd.com/read/27925230/role-of-abc-transporters-in-trans-epithelial-transport-of-vitamin-k-antagonists
#14
Bernadette Espana, Solange Couturier, Caroline Prouillac
Vitamin K antagonists remain (VKAs) the oral anticoagulant of choice of venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study is to assess on cell models the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (phenindione, fluindione)...
December 7, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27887741/evaluation-of-16-genotype-guided-warfarin-dosing-algorithms-in-310-korean-patients-receiving-warfarin-treatment-poor-prediction-performance-in-vkorc1-1173c-carriers
#15
Mina Yang, Rihwa Choi, June Soo Kim, Young Keun On, Oh Young Bang, Hyun-Jung Cho, Soo-Youn Lee
PURPOSE: The purpose of this study was to evaluate the performance of 16 previously published warfarin dosing algorithms in Korean patients. METHODS: The 16 algorithms were selected through a literature search and evaluated using a cohort of 310 Korean patients with atrial fibrillation or cerebral infarction who were receiving warfarin therapy. FINDINGS: A large interindividual variation (up to 11-fold) in warfarin dose was observed (median, 25 mg/wk; range, 7-77 mg/wk)...
December 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27879469/frequency-of-common-vkorc1-polymorphisms-and-their-impact-on-warfarin-dose-requirement-in-pakistani-population
#16
Aisha Qayyum, Muzammil Hasan Najmi, Qaisar Mansoor, Muhammad Irfan, Abdul Khaliq Naveed, Andleeb Hanif, Ali Raza Kazmi, Muhammad Ismail
Polymorphisms in vitamin K epoxide reductase complex subunit 1 (VKORC1) gene lead to interindividual variability in warfarin dose requirement. The characterization of genotype frequency distribution is required in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common VKORC1 polymorphisms to warfarin therapy. A total of 550 stable patients taking warfarin were enrolled after medical history, physical examination, and laboratory investigations...
November 21, 2016: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/27855133/influence-of-genotype-on-warfarin-maintenance-dose-predictions-produced-using-a-bayesian-dose-individualization-tool
#17
Shamin M Saffian, Stephen B Duffull, Rebecca L Roberts, Robert C Tait, Leanne Black, Kirstin A Lund, Alison H Thomson, Daniel F B Wright
BACKGROUND: A previously established Bayesian dosing tool for warfarin was found to produce biased maintenance dose predictions. In this study, we aimed (1) to determine whether the biased warfarin dose predictions previously observed could be replicated in a new cohort of patients from 2 different clinical settings, (2) to explore the influence of CYP2C9 and VKORC1 genotype on predictive performance of the Bayesian dosing tool, and (3) to determine whether the previous population used to develop the kinetic-pharmacodynamic model underpinning the Bayesian dosing tool was sufficiently different from the test (posterior) population to account for the biased dose predictions...
December 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27826798/contribution-of-pharmacogenetic-testing-to-modeled-medication-change-recommendations-in-a-long-term-care-population-with-polypharmacy
#18
Elaine A Sugarman, Ali Cullors, Joel Centeno, David Taylor
BACKGROUND: Among long-term care facility residents, polypharmacy is common, and often appropriate, given the need to treat multiple, complex, chronic conditions. Polypharmacy has, however, been associated with increased healthcare costs, adverse drug events, and drug interactions. The current study evaluates the potential medication cost savings of adding personalized pharmacogenetic information to traditional medication management strategies. METHODS: One hundred and twelve long-term care residents completed pharmacogenetic testing for targeted variants in the following genes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4/CYP3A5, HTR2A, HTR2C, SLC6A4, SLC6A2 COMT, OPRM1, SLCO1B1, VKORC1 and MTHFR...
December 2016: Drugs & Aging
https://www.readbyqxmd.com/read/27824210/vkcfd2-from-clinical-phenotype-to-molecular-mechanism
#19
K J Czogalla, M Watzka, J Oldenburg
Vitamin K 2,3-epoxide reductase complex, subunit 1 (VKORC1) is an enzyme essential for the vitamin K cycle. VKORC1 catalyses the reduction of vitamin K 2,3-epoxide to the quinone form of vitamin K and further to vitamin K hydroquinone. The generated vitamin K hydroquinone serves as substrate for the enzyme γ-glutamyl-carboxylase which modifies all vitamin K-dependent proteins, allowing them to bind calcium ions necessary for physiological activity. Vitamin K-dependent proteins include the coagulation factors FII, FVII, FIX, FX, and proteins C, S und Z...
November 8, 2016: Hämostaseologie
https://www.readbyqxmd.com/read/27789970/pharmacogenetic-polymorphism-as-an-independent-risk-factor-for-frequent-hospitalizations-in-older-adults-with-polypharmacy-a-pilot-study
#20
Joseph Finkelstein, Carol Friedman, George Hripcsak, Manuel Cabrera
Pharmacogenetic testing identifies genetic biomarkers that are predictive of individual sensitivity to particular drugs. A significant proportion of medications that are widely prescribed for older adults are metabolized by enzymes that are encoded by highly polymorphic genes. Pharmacogenetic testing is increasingly used to optimize the medication regimen; however, its potential in older adults with polypharmacy has not been systematically explored. Following the initial case-series study, this study hypothesized that frequently hospitalized older adults with polypharmacy have higher frequency of pharmacogenetic polymorphism as compared to older adults with polypharmacy who are rarely admitted to a hospital...
2016: Pharmacogenomics and Personalized Medicine
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