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https://www.readbyqxmd.com/read/28284562/the-vkorc1-and-cyp2c9-genotypes-significantly-effect-vitamin-k-antagonist-dosing-only-in-patients-over-the-age-of-20years
#1
U Nowak-Göttl, K Dietrich, A Kruempel, C Geisen, L G Mitchell
INTRODUCTION: Given the qualitative differences in the role of VKORC1 and CYP2C9 polymorphisms in Vitamin K antagonists (VKA) dosing variation between adults and children, we were interested in determining at what age these polymorphism begin to play a more significant role. METHODS: A prospective cohort study of 190 patients aged 1-86years receiving VKA for treatment of venous thromboembolism. Blood samples were collected beyond the acute thrombotic event when patients were on stable targeted INR (2-3) for plasma testing and VKORC1/CYP2C9 genotyping...
December 30, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28281786/susceptiveness-of-vitamin-k-epoxide-reductase-complex-subunit-1-gene-polymorphism-in-essential-hypertension
#2
Didem Turgut Cosan, Huseyin Ugur Yazıcı, Emine Colak, Ahu Soyocak, Irfan Degirmenci, Hulyam Kurt, Alparslan Birdane, Ertugrul Colak, Hasan Veysi Gunes
BACKGROUND: Essential hypertension (EH) is defined as worldwide public health problem and one of the important risk factors for development of human coronary artery disease. Increased peripheral arterial resistance is one of the distinguishing characteristics of EH. The extracellular deposition of calcium in the arterial wall is defined as vascular calcification, which results in aortic stiffness and elevation of blood pressure. Regulation of vascular calcification is physiologically limited by γ-carboxylated proteins that regulate mineralization...
March 10, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28262345/influence-of-nr3c1-and-vdr-polymorphisms-on-stable-warfarin-dose-in-patients-with-mechanical-cardiac-valves
#3
Kyung Eun Lee, Jee Eun Chung, Boram Yi, Yoon Jeong Cho, Hyun Jeong Kim, Gwan Yung Lee, Joo Hee Kim, Byung Chul Chang, Hye Sun Gwak
OBJECTIVES: The aim of this study was to evaluate the associations between polymorphisms of VKORC1, CYP2C9, CYP4F2, NR3C1 and VDR genes and stable warfarin doses in Korean patients with mechanical heart valves. METHODS: Seventeen single-nucleotide polymorphisms (SNPs) in 204 patients with stable warfarin dose were analyzed: VKORC1 (rs9934438), CYP2C9 (rs1057910), CYP4F2 (rs2108622), NR3C1 (rs41423247, rs1800445, rs56149945, rs10052957, rs6198, rs33388, rs6196, and rs244465), and VDR (rs1544410, rs11568820, rs731236, rs757343, rs7975232, and rs2228570)...
February 24, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28224948/predictors-of-warfarin-dose-requirements-in-south-african-patients-attending-an-anticoagulation-clinic
#4
Elise Schapkaitz, Johanna Sithole
INTRODUCTION: Warfarin is the most common oral anticoagulant for the treatment and prevention of thromboembolic disease. However, it has a wide interpatient variability in dose requirements due to various genetic and clinical factors. MATERIALS AND METHODS: This study investigated the effect of clinical and genetic factors on the variability of warfarin dose requirements in 147 South African patients (81 white and 66 black). The study was performed at a University Hospital Anticoagulation Clinic managed by nursing sisters at the Charlotte Maxeke Johannesburg Academic Hospital...
March 2017: Journal of Vascular Nursing: Official Publication of the Society for Peripheral Vascular Nursing
https://www.readbyqxmd.com/read/28216623/development-of-a-novel-individualized-warfarin-dose-algorithm-based-on-a-population-pharmacokinetic-model-with-improved-prediction-accuracy-for-chinese-patients-after-heart-valve-replacement
#5
Yu-Bin Zhu, Xian-Hua Hong, Meng Wei, Jing Hu, Xin Chen, Shu-Kui Wang, Jun-Rong Zhu, Feng Yu, Jian-Guo Sun
The gene-guided dosing strategy of warfarin generally leads to over-dose in patients at doses lower than 2 mg/kg, and only 50% of individual variability in daily stable doses can be explained. In this study, we developed a novel population pharmacokinetic (PK) model based on a warfarin dose algorithm for Han Chinese patients with valve replacement for improving the dose prediction accuracy, especially in patients with low doses. The individual pharmacokinetic (PK) parameter - apparent clearance of S- and R-warfarin (CLs) was obtained after establishing and validating the population PK model from 296 recruited patients with valve replacement...
March 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28212442/ecto-5-nucleotidase-cd73-nt5e-vitamin-d-receptor-and-fgf23-gene-polymorphisms-may-play-a-role-in-the-development-of-calcific-uremic-arteriolopathy-in-dialysis-patients-data-from-the-german-calciphylaxis-registry
#6
Hansjörg Rothe, Vincent Brandenburg, Margot Haun, Barbara Kollerits, Florian Kronenberg, Markus Ketteler, Christoph Wanner
INTRODUCTION: Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before. METHODS: We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD)...
2017: PloS One
https://www.readbyqxmd.com/read/28198005/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-pharmacogenetics-guided-warfarin-dosing-2017-update
#7
Julie A Johnson, Kelly E Caudle, Li Gong, Michelle Whirl-Carrillo, C Michael Stein, Stuart A Scott, Ming Ta Michael Lee, Brian F Gage, Stephen E Kimmel, Minoli A Perera, Jeffrey L Anderson, Munir Pirmohamed, Teri E Klein, Nita A Limdi, Larisa H Cavallari, Mia Wadelius
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry...
February 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28164559/conditions-of-high-resolution-melting-analysis-on-the-cobas-z480-instrument-for-the-genotyping-of-vkorc1-in-the-clinical-routine-laboratory
#8
Christian Paar, Verena Hammerl, Hermann Blessberger, Herbert Stekel, Clemens Steinwender
BACKGROUND: High resolution melting (HRM) of amplicons is a simple method for genotyping of single nucleotide polymorphisms (SNPs). Albeit many applications reported, HRM seems to be rarely used in clinical laboratories. The suitability of HRM-PCR for the clinical laboratory was investigated for genotyping of SNPs of the vitamin K epoxide reductase complex unit 1 gene. METHODS: About 100 DNA samples were analyzed by two different HRM-PCRs on the Cobas z480 instrument and compared with a PCR with fluorescently labeled probes (HybProbe-PCR) on the LightCycler 2...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28135054/integrated-analysis-of-genetic-variation-and-gene-expression-reveals-novel-variant-for-increased-warfarin-dose-requirement-in-african-americans
#9
Wenndy Hernandez, Eric R Gamazon, Keston Aquino-Michaels, Erin Smithberger, Travis J O'Brien, Arthur F Harralson, Matthew Tuck, April Barbour, Larisa H Cavallari, Minoli A Perera
BACKGROUND: Warfarin is commonly used to control and prevent thromboembolic disorders. However, due to warfarin's complex dose-requirement relationship, safe and effective use is challenging. Pharmacogenomics-guided warfarin dosing algorithms that include the well-established VKORC1 and CYP2C9 polymorphisms explain only a small proportion of inter-individual variability in African Americans (AAs). OBJECTIVES: We aimed to assess whether transcriptomic analyses could be used to identify regulatory variants associated with warfarin dose response in AAs...
January 30, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079798/clinical-and-genetic-factors-associated-with-warfarin-maintenance-dose-in-northern-chinese-patients-with-mechanical-heart-valve-replacement
#10
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
#11
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
#12
E V Baranova, T I Verhoef, G Ragia, S le Cessie, F W Asselbergs, A de Boer, V G Manolopoulos, A H Maitland-van der Zee
Essentials Prospective studies of pharmacogenetic-guided (PG) coumarin dosing produced varying results. EU-PACT acenocoumarol and phenprocoumon trials compared PG and non-PG dosing algorithms. Sub-analysis of EU-PACT identified differences between trial arms across VKORC1-CYP2C9 groups. Adjustment of the PG algorithm might lead to a higher benefit of genotyping. SUMMARY: Background The multicenter, single-blind, randomized EU-PACT trial compared the safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep vein thrombosis...
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
#13
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
#14
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
#15
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
#16
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
#17
Wei Tang, Qing-ping Shi, Feng Ding, Mei-Ling Yu, Jian 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...
December 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
#18
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
#19
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
#20
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
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