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https://www.readbyqxmd.com/read/28502675/genotype-guided-dosing-of-warfarin-through-modeling-and-simulation
#1
Jiexin Deng, Valvanera Vozmediano Esteban, Monica Rodriguez, Larisa H Cavallari, Stephan Schmidt
Current genotype-guided algorithms for warfarin dosing fail to deliver optimal performance in two aspects: 1) these algorithms are not able to achieve the same level of benefits in non-white populations, since they were developed based on multivariate regression analysis with mostly European/White data and did not include genetic variants found frequently in non-white populations; 2) these algorithms do not account for the dynamic dose/response relationship and were limited in their usefulness to guide dosing during the initiation phase, as the possession of variant VKORC1 and/or CYP2C9 polymorphisms has been associated with a more rapid attainment of target international normalized ratio (INR) and higher risk of over-anticoagulation even in genotype-guided patients...
May 11, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28479094/integrating-genotypes-in-the-same-tt2r2-score-for-the-prediction-of-anticoagulation-control-in-chinese-patients-with-atrial-fibrillation-on-warfarin
#2
Jia Liu, Nina Wang, Liuan Qin, Jun Liu, Shaozhi Xi, Xuyun Wang, Xiaoqi Li, Yuxiao Zhang, Tong Yin
INTRODUCTION: The SAMe-TT2R2 score has been proposed to predict whether patients with atrial fibrillation (AF) would be well anti-coagulated with warfarin or not. However, it might over-estimate the number of patients under suboptimal warfarin treatment in non-Caucasians. This study was designed to modify the SAMe-TT2R2 score with genotypes and validate it in Chinese AF patients treated with warfarin. MATERIAL AND METHODS: Consented Chinese-Han patients (n=510) with AF under the treatment of warfarin for at least 3months were randomly divided into a derivation (n=310) and a validation cohort (n=200)...
April 29, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28429387/the-association-between-ggcx-mir-133-genetic-polymorphisms-and-warfarin-stable-dosage-in-han-chinese-patients-with-mechanical-heart-valve-replacement
#3
X-Y Tang, J Zhang, J Peng, S-L Tan, W Zhang, G-B Song, L-M Liu, C-L Li, H Ren, L Zeng, Z-Q Liu, X-P Chen, X-M Zhou, H-H Zhou, J-X Hu, Z Li
WHAT IS KNOWN AND OBJECTIVE: Warfarin is a widely used anticoagulant with a narrow therapeutic index. Polymorphisms in the VKORC1, CYP2C9 and CYP4F2 genes have been verified to correlate with warfarin stable dosage (WSD). Whether any other genes or variants affect the dosage is unknown. The aim of our study was to investigate the relationship between GGCX, miR-133 variants and the WSD in Han Chinese patients with mechanical heart valve replacement (MHVR). METHODS: A total of 231 patients were enrolled in the study...
April 21, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28428867/adaptative-evolution-of-the-vkorc1-gene-in-mus-musculus-domesticus-is-influenced-by-the-selective-pressure-of-anticoagulant-rodenticides
#4
Joffrey Goulois, Véronique Lambert, Lionel Legros, Etienne Benoit, Virginie Lattard
Anticoagulant rodenticides are commonly used to control rodent pests worldwide. They specifically inhibit the vitamin K epoxide reductase (VKORC1), which is an enzyme encoded by the Vkorc1 gene, involved in the recycling of vitamin K. Therefore, they prevent blood clotting. Numerous mutations of Vkorc1 gene were reported in rodents, and some are involved in the resistant to rodenticides phenotype. Two hundred and sixty-six mice tails were received from 65 different locations in France. Coding sequences of Vkorc1 gene were sequenced in order to detect mutations...
April 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28412319/genetic-and-non-genetic-factors-affecting-the-quality-of-anticoagulation-control-and-vascular-events-in-atrial-fibrillation
#5
Yun Kyung Park, Mi Ji Lee, Jae Ha Kim, Jin Soo Lee, Rae Woong Park, Gyeong-Moon Kim, Chin-Sang Chung, Kwang Ho Lee, June Soo Kim, Soo-Youn Lee, Oh Young Bang
BACKGROUND: Warfarin has a narrow therapeutic window. We hypothesized that genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1) would show stronger associations than modifiable factors with the quality of anticoagulation control and risks for thromboembolism and hemorrhage. METHODS: In this retrospective cohort analysis, clinical and genetic data were collected from 380 patients with atrial fibrillation (AF) who were followed for an average observation period of 4 years...
April 12, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28408837/polymorphisms-of-vkorc1-and-cyp2c9-are-associated-with-warfarin-sensitivity-in-chinese-population
#6
LiQun Jia, Zanxin Wang, Jianlong Men, Heng Cai, Minxin Wei
OBJECTIVE: Warfarin is a commonly prescribed anticoagulant for prevention of thromboembolic events. Wide inter-individual dose variation, narrow therapeutic range and risk of serious bleeding result in difficulties in achieving the therapeutic effect. The present study was designed to clarify the real biological significance of the polymorphisms of VKORC1 and cytochrome P450 2C9 (CYP2C9) in warfarin metabolism. METHODS: A total of 214 patients with warfarin anticoagulant therapy were selected...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28401802/the-impact-of-gene-polymorphisms-on-anticoagulation-control-with-warfarin
#7
Hai He Jiang, Jia Liu, Yi Chen Wang, Hui Ming Ye, Xi Li, Ya Xing Zhou, Wei Zhang, Lian Sheng Wang
Differences in warfarin maintenance dosages based on the presence of polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through dosage adjustment according to routine guidelines. Little is known about whether routine therapy could provide consensus anticoagulation control for patients with different genotypes. This study was carried out to compare anticoagulant control in patients with different genotypes. Six hundred seventy patients using warfarin according to Chinese guidelines were enrolled...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28388432/large-diverse-population-cohorts-of-hipscs-and-derived-hepatocyte-like-cells-reveal-functional-genetic-variation-at-blood-lipid-associated-loci
#8
Evanthia E Pashos, YoSon Park, Xiao Wang, Avanthi Raghavan, Wenli Yang, Deepti Abbey, Derek T Peters, Juan Arbelaez, Mayda Hernandez, Nicolas Kuperwasser, Wenjun Li, Zhaorui Lian, Ying Liu, Wenjian Lv, Stacey L Lytle-Gabbin, Dawn H Marchadier, Peter Rogov, Jianting Shi, Katherine J Slovik, Ioannis M Stylianou, Li Wang, Ruilan Yan, Xiaolan Zhang, Sekar Kathiresan, Stephen A Duncan, Tarjei S Mikkelsen, Edward E Morrisey, Daniel J Rader, Christopher D Brown, Kiran Musunuru
Genome-wide association studies have struggled to identify functional genes and variants underlying complex phenotypes. We recruited a multi-ethnic cohort of healthy volunteers (n = 91) and used their tissue to generate induced pluripotent stem cells (iPSCs) and hepatocyte-like cells (HLCs) for genome-wide mapping of expression quantitative trait loci (eQTLs) and allele-specific expression (ASE). We identified many eQTL genes (eGenes) not observed in the comparably sized Genotype-Tissue Expression project's human liver cohort (n = 96)...
April 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28384046/cross-validation-of-high-resolution-melting-analysis-based-genotyping-platform
#9
Taimour Langaee, Lynda Stauffer, Cheryl Galloway, Mohamed H Solayman, Larisa Cavallari
AIMS: Developing genetic and pharmacogenetic panels enhances genetic testing in clinical molecular diagnostics and precision medicine. This study was designed to cross-validate the performance of Canon's multiplex high-resolution DNA melting analysis platform with the Applied Biosystems TaqMan(®)-based Quant Studio Real-Time PCR System and Pyrosequencing(®) genotyping platforms for common genetic polymorphisms of the vitamin K epoxide reductase complex 1 (VKORC1) and CYP2C9. MATERIALS AND METHODS: Genomic DNA isolated from 240 blood and saliva samples was used to genotype the VKORC1-1639 G/A (rs9923231), CYP2C9*2 (430C>T, rs28371674), and CYP2C9*3 (1075A>C, rs1057910) single-nucleotide polymorphisms (SNPs) on the three above-mentioned genotyping platforms...
April 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28382498/assessing-the-relative-potency-of-s-and-r-warfarin-with-a-new-pk-pd-model-in-relation-to-vkorc1-genotypes
#10
Myriam Ferrari, Vittorio Pengo, Massimiliano Barolo, Fabrizio Bezzo, Roberto Padrini
PURPOSE: The purpose of this study is to develop a new pharmacokinetic-pharmacodynamic (PK-PD) model to characterise the contribution of (S)- and (R)-warfarin to the anticoagulant effect on patients in treatment with rac-warfarin. METHODS: Fifty-seven patients starting warfarin (W) therapy were studied, from the first dose and during chronic treatment at INR stabilization. Plasma concentrations of (S)- and (R)-W and INRs were measured 12, 36 and 60 h after the first dose and at steady state 12-14 h after dosing...
April 5, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28376131/dietary-and-genetic-influences-on-hemostasis-in-a-yup-ik-alaska-native-population
#11
Nicholas T Au, Morayma Reyes, Bert B Boyer, Scarlett E Hopkins, Jynene Black, Diane O'Brien, Alison E Fohner, Joe Yracheta, Timothy Thornton, Melissa A Austin, Wylie Burke, Kenneth E Thummel, Allan E Rettie
Fish and marine animals are important components of the subsistence diet of Alaska Native people, resulting in a high ω3 PUFA intake. The historical record for circumpolar populations highlights a tendency for facile bleeding, possibly related to ω3 PUFA effects on platelet activation and/or vitamin K-dependent clotting factors. To evaluate these two scenarios in Yup'ik people of southwestern Alaska, we examined the association between dietary ω3 PUFA intake and activities of clotting factor II, V, fibrinogen, PT, INR, PTT, and sP-selectin in 733 study participants, using the nitrogen isotope ratio of red blood cells as a biomarker of ω3 PUFA consumption...
2017: PloS One
https://www.readbyqxmd.com/read/28371488/bioequivalence-study-of-warfarin-in-healthy-chinese-volunteers-with-a-validated-high-performance-liquid-chromatography-mass-spectrometry-method
#12
Wenlong Li, Fanlong Bu, Rong Li, Benjie Wang, Abdul Sami Shaikh, Yunyun Zhang, Ruichen Guo, Rui Zhang
This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.5 mg of innovative film-coated warfarin sodium tablets or the marketed sugar-coated warfarin sodium tablets. Blood samples were collected at different time points after dosing for investigation of the pharmacokinetics of warfarin in human plasma...
April 3, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28338108/vkorc1-1639-g-a-polymorphism-and-the-risk-of-non-variceal-upper-gastrointestinal-bleeding
#13
Ioana Groza, Dana Matei, Marcel Tantau, Adrian P Trifa, Sorin Crisan, Stefan C Vesa, Corina Bocsan, Anca D Buzoianu, Monica Acalovschi
BACKGROUND AND AIMS: The mutations in the gene that encodes vitamin K epoxide reductase (VKOR) enzyme are responsible for low levels of vitamin K. The purpose of this study was to evaluate whether the presence of the VKORC1 -1639 G> A polymorphism is a risk factor for non-variceal upper gastrointestinal bleeding (UGIB) in patients without concomitant therapy with vitamin K antagonists. METHODS: This case-control study comprised 163 consecutive patients diagnosed with UGIB and 178 controls, in whom the diagnosis of UGIB was excluded...
March 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
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
#14
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
#15
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 a 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...
May 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
#16
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
#17
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
#18
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
#19
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
#20
J A Johnson, K E Caudle, L Gong, M Whirl-Carrillo, C M Stein, S A Scott, M T Lee, B F Gage, S E Kimmel, M A Perera, J L Anderson, M Pirmohamed, T E Klein, N A Limdi, L H Cavallari, M 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
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