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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/28074382/engaging-hmong-adults-in-genomic%C3%A2-and%C3%A2-pharmacogenomic-research-toward-reducing-health-disparities-in-genomic-knowledge-using-a-community-based-participatory-research-approach
#2
Kathleen A Culhane-Pera, Robert J Straka, MaiKia Moua, Youssef Roman, Pachia Vue, Kang Xiaaj, May Xia Lo, Mai Lor
Advancing precision medicine relies in part on examining populations that may exhibit unique genetic variants that impact clinical outcomes. Failure to include diverse populations in genomic-based research represents a health disparity. We implemented a community-based participatory research (CBPR) process with the Hmong community in Minnesota, who were refugees from Laos, in order to assess the feasibility of conducting genomic and pharmacogenomic-based research for genetic variants that are relevant to the Hmong community...
January 10, 2017: Journal of Community Genetics
https://www.readbyqxmd.com/read/28058824/the-effect-of-amiodarone-on-warfarin-anticoagulation-a-register-based-nationwide-cohort-study-involving-the-swedish-population
#3
Johan Holm, Jonatan D Lindh, Marine L Andersson, Buster Mannheimer
BACKGROUND: Data indicate that the interaction between warfarin and amiodarone results in increased warfarin effect. There are several large, well-performed studies using genetic and clinical factors such as comedication to predict an adequate starting dose of warfarin. However, longitudinal data on the effect of introducing amiodarone in patients on an ongoing warfarin regime are more scarce. OBJECTIVES: An investigation of how initiation of amiodarone affects the anticoagulant effect and dosing of warfarin, using data from three nation-wide registries...
January 6, 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/27999513/choosing-non-vitamin-k-antagonist-oral-anticoagulants-practical-considerations-we-need-to-know
#5
REVIEW
Alpesh Amin
BACKGROUND: Warfarin is a well-established agent for use in the prevention of stroke or systemic embolic event (SEE) in patients with nonvalvular atrial fibrillation (NVAF) and for the treatment of venous thromboembolism (VTE). However, management of patients requiring oral anticoagulation with warfarin can be complicated by the need for frequent monitoring, drug-drug and drug-food interactions, and a variable response based on genetic polymorphisms. The non-vitamin K antagonist oral anticoagulants (NOACs) were developed as alternatives to warfarin; they do not require routine monitoring and have predictable pharmacokinetics, fewer drug-drug interactions, and limited drug-food interactions...
2016: Ochsner Journal
https://www.readbyqxmd.com/read/27992547/the-impact-of-genetic-and-non-genetic-factors-on-warfarin-dose-prediction-in-mena-region-a-systematic-review
#6
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
#7
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/27938396/genetic-polymorphisms-of-patients-on-stable-warfarin-maintenance-therapy-in-a-ghanaian-population
#8
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
#9
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/27879469/frequency-of-common-vkorc1-polymorphisms-and-their-impact-on-warfarin-dose-requirement-in-pakistani-population
#10
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/27878474/quantitative-assessment-of-cyp2c9-genetic-polymorphisms-effect-on-the-oral-clearance-of-s-warfarin-in-healthy-subjects
#11
Chanan Shaul, Simcha Blotnick, Mordechai Muszkat, Meir Bialer, Yoseph Caraco
BACKGROUND: Genetic polymorphisms in CYP2C9 account for 10-20% of the variability in warfarin dose requirement. As such CYP2C9 genetic polymorphisms are commonly included in algorithms aimed to optimize warfarin therapy as a way to account for variability in warfarin responsiveness that is due to altered pharmacokinetics. However, most of the currently available pharmacokinetic data were derived from studies among patients on chronic warfarin therapy and therefore suffer from the confounding effects of disease states and drug interactions...
November 22, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27864383/use-of-pharmacogenetic-information-in-the-treatment-of-cardiovascular-disease
#12
REVIEW
Kevin Friede, Josephine Li, Deepak Voora
BACKGROUND: In 1964, Robert A. O'Reilly's research group identified members of a family who required remarkably high warfarin doses (up to 145 mg/day, 20 times the average dose) to achieve appropriate anticoagulation. Since this time, pharmacogenetics has become a mainstay of cardiovascular science, and genetic variants have been implicated in several fundamental classes of medications used in cardiovascular medicine. CONTENT: In this review, we discuss genetic variants that affect drug response to 3 classes of cardiovascular drugs: statins, platelet P2Y12 inhibitors, and anticoagulants...
January 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/27864202/implementation-of-inpatient-models-of-pharmacogenetics-programs
#13
Larisa H Cavallari, Craig R Lee, Julio D Duarte, Edith A Nutescu, Kristin W Weitzel, George A Stouffer, Julie A Johnson
PURPOSE: The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided drug therapy in pharmacogenetics programs at three institutions is highlighted. SUMMARY: Pharmacists are well positioned to assume important roles in facilitating the clinical use of genetic information to optimize drug therapy given their expertise in clinical pharmacology and therapeutics...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27855643/evaluation-of-a-pharmacogenetic-based-warfarin-dosing-algorithm-in-patients-with-low-time-in-therapeutic-range-study-protocol-for-a-randomized-controlled-trial
#14
Leiliane Rodrigues Marcatto, Luciana Sacilotto, Carolina Tosin Bueno, Mirella Facin, Celia Maria Cassaro Strunz, Francisco Carlos Costa Darrieux, Maurício Ibrahim Scanavacca, Jose Eduardo Krieger, Alexandre Costa Pereira, Paulo Caleb Junior Lima Santos
BACKGROUND: Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding events. Recently, we developed a pharmacogenetic-based warfarin dosing algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a tertiary cardiovascular hospital...
November 17, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27855133/influence-of-genotype-on-warfarin-maintenance-dose-predictions-produced-using-a-bayesian-dose-individualization-tool
#15
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/27816002/strain-differences-in-intestinal-toxicity-of-warfarin-in-rats
#16
Ivana Mirkov, Aleksandra Popov Aleksandrov, Marina Ninkov, Dina Mileusnic, Jelena Demenesku, Lidija Zolotarevski, Vesna Subota, Debora Stefik, Dragan Kataranovski, Milena Kataranovski
Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is among adverse effects of therapy in humans. Having in mind genetic variations in the effectiveness of WF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinal toxicity of oral warfarin in rats were examined in this study. High WF dose (3.5mg/l) led to mortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher values of prothrombin time were noted at low WF dose (0...
December 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27768243/prenatal-exposure-to-environmental-factors-and-congenital-limb-defects
#17
Peter G Alexander, Karen L Clark, Rocky S Tuan
Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact...
October 21, 2016: Birth Defects Research. Part C, Embryo Today: Reviews
https://www.readbyqxmd.com/read/27752976/pharmacogenomics-and-pharmacogenetics-for-the-intensive-care-unit-a-narrative-review
#18
Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
January 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/27743182/linkage-disequilibrium-between-the-cyp2c19-2-17-and-cyp2c9-1-alleles-and-impact-of-vkorc1-cyp2c9-cyp2c19-gene-polymorphisms-and-gene-gene-interactions-on-warfarin-therapy
#19
Koroush Khalighi, Gang Cheng, Seyedabbas Mirabbasi, Bahar Khalighi, Yin Wu, Wuqiang Fan
Warfarin therapy is complicated by its large inter-individual and intra-individual variability. Both genetic and non-genetic factors can affect warfarin therapy. This study aims to investigate the allele distribution of VKORC1, CYP2C9 and CYP2C19, contribution of different allele variants and possible gene-gene interaction on warfarin therapy. Four hundreds and ninety-two patients were enrolled and single nucleotide polymorphisms for vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 CYP2C9 and cytochrome P450 CYP2C19 were genotyped...
October 14, 2016: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/27740732/identification-of-novel-variants-associated-with-warfarin-stable-dosage-by-use-of-a-two-stage-extreme-phenotype-strategy
#20
Z Luo, X Li, M Zhu, J Tang, Z Li, X Zhou, G Song, Z Liu, H Zhou, W Zhang
: Essentials Required warfarin doses for mechanical heart valves vary greatly. A two-stage extreme phenotype design was used to identify novel warfarin dose associated mutation. We identified a group of variants significantly associated with extreme warfarin dose. Four novel identified mutations account for 2.2% of warfarin dose discrepancies. SUMMARY: Background The variation among patients in warfarin response complicates the management of warfarin therapy, and an improper therapeutic dose usually results in serious adverse events...
October 14, 2016: Journal of Thrombosis and Haemostasis: JTH
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