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Sylvie Perreault, Payman Shahabi, Robert Côté, Stéphanie Dumas, Étienne Rouleau-Mailloux, Yassamin Feroz Zada, Sylvie Provost, Ian Mongrain, Marc Dorais, Thao Huynh, Simon Kouz, Ariel Diaz, Mark Blostein, Simon de Denus, Jacques Turgeon, Jeffrey Ginsberg, Jacques Lelorier, Lyne Lalonde, Lambert Busque, Jeannine Kassis, Mario Talajic, Jean-Claude Tardif, Marie-Pierre Dubé
BACKGROUND: Over- and under-coagulation with warfarin is associated with hemorrhagic and thromboembolic events, respectively. Genetic and clinical factors affect warfarin response, and the causes of this variability remain unclear. We present descriptive statistics and test for predictors of poor anticoagulation control. METHODS: The Quebec Warfarin Cohort (QWC) comprises 1,059 new warfarin users, with prospective follow up using telephone questionnaires every 3 months for one year, and using healthcare administrative databases (RAMQ and Med-Echo) for 5-year prior to cohort entry and up to 10-years following active patient participation...
March 15, 2018: Clinical Cardiology
Jean Mooney, Mark R Lynch, Colin V Prescott, Tracy Clegg, Michael Loughlin, Bernard Hannon, Colm Moore, Richard Faulkner
While resistance to anticoagulant rodenticides is known to occur in many European populations of Norway rat and house mouse, to-date no data is available on the occurrence in Ireland of such resistance. No genetic evidence for the occurrence of resistance was found in 65 Norway rat samples analysed, indicative of an absence, or low prevalence, of resistance in rats in at least the Eastern region of the island of Ireland. The presence of two of the most commonly found amino acid substitutions Leu128Ser and Tyr139Cys associated with house mouse resistance to anticoagulant rodenticides was confirmed...
March 14, 2018: Scientific Reports
Carrie C Hoefer, Emily J Brick, Ann Savariar, David F Kisor, Amy Dawson, Ahmad Khatri, Brian Henriksen
AIM: The aim of this study was to investigate 60 SNPs pertaining to drug metabolism and pharmacodynamics in the Burmese refugee population in the Fort Wayne, Indiana area to better inform patient care. MATERIALS & METHODS: Sixty-two self-identified Burmese refugees were genotyped for 60 common SNPs pertaining to pharmacokinetic and pharmacodynamic pharmacogenes. The resulting allelic frequencies were compared with Ensembl's database for surrounding populations to Myanmar and America...
March 8, 2018: Pharmacogenomics
Ksenija Makar-Aušperger, Kristina Krželj Cand Med, Martina Lovrić Benčić, Matea Radačić Aumiler, Viktorija Erdeljić Turk, Nada Božina
BACKGROUND: Observational studies have indicated potential benefits of CYP2C9 and VKORC1 guided dosing of warfarin but randomized clinical trials have resulted in contradictory findings. One of the reasons for contradiction may be the negligence of possible differences between warfarin indications. This study aims to determine efficacy and safety of genotype- and clinically guided dosing of warfarin in atrial fibrillation (AF), deep-vein thrombosis (DVT), and pulmonary embolism (PE) within the first five days after the introduction of therapy...
February 27, 2018: Therapeutic Drug Monitoring
Marwa Ajmi, Asma Omezzine, Slim Achour, Dorra Amor, Haithem Hamdouni, Fatma Ben Fredj Ismaïl, Nabila Ben Rejeb, Chedia Laouani Kechrid, Essia Boughzela, Ali Bouslama
PURPOSE: We aimed to study potential variables involved in interindividual variability to acenocoumarol (AC) response in order to establish a pharmacogenetic algorithm (PA) that includes clinical and genetic factors to predict adequate AC dose to stabilize anticoagulation in a cohort of Tunisian patients. METHODS: Genotyping of the CYP2C9, VKORC1, CYP4F2, and CALU polymorphisms was conducted on 246 patients using PCR-RFLP technique. AC normalized maintenance dose (NMD): ((mean maintenance dose/international normalized ratio (INR)) equilibrium) was calculated...
February 26, 2018: European Journal of Clinical Pharmacology
Cansu Ozbayer, Hulyam Kurt, Medine Nur Kebapci, Didem Turgut Cosan, Ertugrul Colak, Hasan Veysi Gunes, Irfan Degirmenci
The vitamin K epoxide reductase complex subunit 1 (VKORC1) gene is expressed in many tissue types, and encodes the VKORC1 protein, which is a key enzyme in the vitamin K cycle. Although researchers have focused on the effects of vitamin K on glucose metabolism, and on its role in the development of type 2 diabetes (T2DM), no consensus has yet been reached. Therefore, here we aimed to investigate the association between VKORC1 variants and the risk of T2DM. The 3673G / A (rs9923231) and 9041G / A (rs7294) VKORC1 variants were investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 100 control individuals and 100 patients with T2DM...
February 22, 2018: International Journal for Vitamin and Nutrition Research. Journal International de Vitaminologie et de Nutrition
Faruk Kutluturk, Ahmet Inanir, Aydın Rustemoglu, Suheyla Kaya, Ayse Kevser Demir, Gul Dursun, Serbulent Yigit
Introductıon: Osteoporosis is a common disease, and several factors contribute to its development. Recently, there has been increasing evidence that vitamin K (VK) plays a critical role in maintaining bone strength. Vitamin K serves as a co-factor for the γ-carboxylation of particular proteins to convert specific glutamic acid residues to γ-carboxyglutamic acid residues. This process involves two enzymes, γ-glutamyl carboxylase and vitamin K epoxide reductase (VKORC1). The number of studies investigating the effects of VKORC1 gene mutations on bone mineral density in postmenopausal osteoporosis patients is limited...
February 11, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Agata Hanna Bryk, Ewa Wypasek, Krzysztof Plens, Magdalena Awsiuk, Anetta Undas
INTRODUCTION: Single nucleotide polymorphisms (SNP) in genes encoding proteins involved in metabolism and action of vitamin K antagonists (VKA) affect anticoagulation stability. We investigated how those polymorphisms influence bleeding rates in patients following venous thromboembolism (VTE). MATERIALS AND METHODS: In 324 patients following unprovoked VTE, 143 (44%) on warfarin and 181 (56%) on acenocoumarol, we recorded bleedings within the preceding 24 months...
February 9, 2018: Vascular Pharmacology
Yongxian Wan, Lili Xu, Naiqiang Zhuo, Xiaobo Lu
Reports have indicated that warfarin is the most widely prescribed anticoagulant. However, traditionally prescribed doses for each patient may be too low or too high. The therapeutic effect is often hindered by a lack of evidence-based medical information. Herein, our aim is to provide this information. To accomplish this challenge, we report the development of a novel assay based on biotinylated tetrahedral DNA as a capture probe and fullerene (C60)-based nanomaterial as a redox probe using an ultrasensitivity assay with the Vitamin K epoxide reductase complex, subunit 1 (VKORC1)...
June 7, 2018: Analytica Chimica Acta
Carlo Federico Zambon, Vittorio Pengo, Stefania Moz, Dania Bozzato, Paola Fogar, Andrea Padoan, Mario Plebani, Francesca Groppa, Giovanni De Rosa, Roberto Padrini
PURPOSE: A previous trial failed to demonstrate the superiority of a demographic-genetic algorithm in predicting warfarin (W) dose over a standard clinical approach. The purpose of the present study is to re-analyse the results in subgroups of patients with differing baseline sensitivity to W, integrated with additional pharmacokinetic data. METHODS: The original trial allocated 180 treatment-naïve patients with non-valvular atrial fibrillation to a control arm (CTL, n = 92) or a genetic-guided arm (GEN, n = 88)...
February 2, 2018: European Journal of Clinical Pharmacology
Mengdan Yan, Dianzhen Li, Guige Zhao, Jing Li, Fanglin Niu, Bin Li, Peng Chen, Tianbo Jin
INTRODUCTION: Drug response and target therapeutic dosage are different among individuals. The variability is largely genetically determined. With the development of pharmacogenetics and pharmacogenomics, widespread research have provided us a wealth of information on drug-related genetic polymorphisms, and the very important pharmacogenetic (VIP) variants have been identified for the major populations around the world whereas less is known regarding minorities in China, including the Yi ethnic group...
January 11, 2018: Gene
Julie Lacombe, Mark A Rishavy, Kathleen L Berkner, Mathieu Ferron
Vertebrates possess 2 proteins with vitamin K oxidoreductase (VKOR) activity: VKORC1, whose vitamin K reduction supports vitamin K-dependent (VKD) protein carboxylation, and VKORC1-like 1 (VKORC1L1), whose function is unknown. VKD proteins include liver-derived coagulation factors, and hemorrhaging and lethality were previously observed in mice lacking either VKORC1 or the γ-glutamyl carboxylase (GGCX) that modifies VKD proteins. Vkorc1-/- mice survived longer (1 week) than Ggcx-/- mice (midembryogenesis or birth), and we assessed whether VKORC1L1 could account for this difference...
January 11, 2018: JCI Insight
L Colàs-Campàs, J L Royo, M V Montserrat, C Marzo, J Molina-Seguín, I Benabdelhak, S Cambray, F Purroy
Oral anticoagulant treatments, such as vitamin K antagonists (VKAs), are the main treatments administered to atrial fibrillation (AF) patients in order to prevent ischemic stroke (IS). However, the genes involved in the VKA metabolism can undergo variations in a single nucleotide (SNP). These SNPs may then affect the VKA target enzyme (VKORC1), VKA degradation enzyme (CYP2C9), and vitamin K bioavailability enzyme (CYP4F2). We genotyped these SNPs in a cohort of patients with non-valvular AF who were under VKA treatment after suffering an IS...
December 22, 2017: Pharmacogenomics Journal
Liang-Liang Cai, Wen-Qing Huang, Zhi-Ying Su, Hui-Ming Ye, Lian-Sheng Wang, Yuan Wu, Zhong-Ying Zhang, Wei Zhang, Chi-Meng Tzeng
Warfarin is a commonly prescribed and effective oral anticoagulant. Genetic polymorphisms associated with warfarin metabolism and sensitivity have been implicated in the wide inter-individual dose variation that is observed. Several algorithms integrating patients' clinical characteristics and genetic polymorphism information have been explored to predict warfarin dose. However, most of these algorithms could explain only over half of the variation in a warfarin maintenance dose, suggesting that additional genetic factors may exist and need to be identified...
December 12, 2017: Scientific Reports
Fatima Donia Mili, Tenecia Allen, Paula Weinstein Wadell, W Craig Hooper, Christine De Staercke, Christopher J Bean, Cathy Lally, Harland Austin, Nanette K Wenger
AIM: The study objectives were to investigate the association between selected CYP2C9 and VKORC1 single nucleotide polymorphisms with serious bleeding or thrombotic risk, and to estimate mean daily maintenance dose of warfarin and international normalized ratio measurements among Blacks receiving warfarin anticoagulation. METHODS: We conducted a retrospective cohort study among 230 Black adults receiving warfarin for a minimum of three consecutive months with a confirmed date of first dosage...
January 2018: Future Cardiology
Vanessa Gonzalez-Covarrubias, Javier Urena-Carrion, Beatriz Villegas-Torres, J Eduardo Cossío-Aranda, Sergio Trevethan-Cravioto, Raul Izaguirre-Avila, O Javier Fiscal-López, Xavier Soberon
Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS , and GGCX, VKORC1, CYP2C18, NQO1 . A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, CYP1A1, CYP3A4, CYP3A5 , and F8 , and a low proportion of novel-to-known variants on CYP2E1, VKORC1 , and SULT1A1/2 ...
2017: Frontiers in Pharmacology
Sajad Rafiee, Masoumeh Rajabibazl, Reza Meshkani, Azam Daraei, Mehryar Zargari, Fahimeh Sharafeddin, Zahra Fazeli, Attabak Toffani Milani, Maryam Taherkhani
Warfarin is a vitamin K antagonist that genetic and non-genetic factors affected on its dose requirement in the patients with cardio vascular disease. The aim of this study was whether the APOE and VKORC1 polymorphisms influence on warfarin dose requirements in the part of Iranian patients. Blood samples were collected from 86 warfarin-treated patients. After extraction of genomic DNA, the VKORC1 (rs9923231) and the APOE (rs429358 and rs7412) polymorphisms were genotyped by PCR-RFLP technique. We found that the Iranian patients carrying genotypes GA or AA of VKORC1 polymorphism tended to receive lower dose of warfarin (p = 0...
2017: Iranian Journal of Pharmaceutical Research: IJPR
Negin Farzamikia, Ebrahim Sakhinia, Abbas Afrasiabirad
Many lines of evidence suggest that warfarin dosing variability is significantly associated with cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles. Therefore, we investigated the influence of CYP2C9*2 (430C/T), *3 (1075A/C) and VKORC1 (-1639G/A) polymorphisms on warfarin dose requirements in patients who underwent cardiac valve surgery during the postoperative period.A total of 100 patients with heart valve replacement who had a prescribed target international normalized ratio (INR) range of 2-3 were enrolled in the study...
December 22, 2017: Laboratory Medicine
Chandrama Mukherjee, Kevin M Sweet, Jasmine A Luzum, Mahmoud Abdel-Rasoul, Michael F Christman, Joseph P Kitzmiller
Aim: This study aimed to examine pharmacogenomic test results and patient perspectives at an academic cardiovascular medicine clinic. Patients & methods: Test results for three common cardiovascular drug-gene tests (warfarin- CYP2C9-VKORC1 , clopidogrel- CYP2C19 and simvastatin- SLCO1B1 ) of 208 patients in the Ohio State University-Coriell Personalized Medicine Collaborative were examined to determine the incidence of potentially actionable test results. A post-hoc, anonymous, patient survey was also conducted...
September 2017: Personalized Medicine
Nian-Xin Jiang, Ying-Hui Xu, Jing-Wen Xia, Bing Jiang, Yan-Song Li
Background/aim: Warfarin is a common anticoagulant with large interindividual differences and a narrow therapeutic range. The polymorphisms of gamma-glutamyl carboxylase (GGCX) are important genetic factors for warfarin dose requirements. Materials and methods: Polymerase chain reaction and direct sequencing methods were used to detect the GGCX rs699664 genotype in 215 atrial fibrillation (AF) patients with warfarin administration. The effects on warfarin dose by different genotypes were analyzed. A warfarin dosing algorithm was developed based on age, height, CYP2C9, VKORC1, and GGCX genotype...
August 23, 2017: Turkish Journal of Medical Sciences
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