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https://www.readbyqxmd.com/read/29337087/genetic-polymorphisms-of-pharmacogenomic-vip-variants-in-the-yi-population-from-china
#1
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
https://www.readbyqxmd.com/read/29321368/vkor-paralog-vkorc1l1-supports-vitamin-k-dependent-protein-carboxylation-in-vivo
#2
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
https://www.readbyqxmd.com/read/29273767/the-rs2108622-polymorphism-is-related-to-the-early-risk-of-ischemic-stroke-in-non-valvular-atrial-fibrillation-subjects-under-oral-anticoagulation
#3
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
https://www.readbyqxmd.com/read/29234073/identification-of-two-novel-genes-slc15a2-and-slco1b3-associated-with-maintenance-dose-variability-of-warfarin-in-a-chinese-population
#4
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
https://www.readbyqxmd.com/read/29218998/vkorc1-1639a-allele-influences-warfarin-maintenance-dosage-among-blacks-receiving-warfarin-anticoagulation-a-retrospective-cohort-study
#5
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...
December 8, 2017: Future Cardiology
https://www.readbyqxmd.com/read/29218011/pharmacogenetic-variation-in-over-100-genes-in-patients-receiving-acenocumarol
#6
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
https://www.readbyqxmd.com/read/29201112/association-of-warfarin-therapy-with-apoe-and-vkorc1-genes-polymorphism-in-iranian-population
#7
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
https://www.readbyqxmd.com/read/29182754/pharmacogenetics-based-warfarin-dosing-in-patients-with-cardiac-valve-replacement-the-effects-of-cyp2c9-and-vkorc1-gene-polymorphisms
#8
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...
November 22, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29181084/clinical-pharmacogenomics-patient-perspectives-of-pharmacogenomic-testing-and-the-incidence-of-actionable-test-results-in-a-chronic-disease-cohort
#9
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
https://www.readbyqxmd.com/read/29156869/impact-of-ggcx-polymorphisms-on-warfarin-dose-requirements-in-atrial-fibrillation-patients
#10
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
https://www.readbyqxmd.com/read/29155484/elevated-difenacoum-metabolism-involved-in-the-difenacoum-resistant-phenotype-observed-in-berkshire-rats-homozygous-for-the-l120q-mutation-in-vkorc1-gene
#11
Maylis Boitet, Abdessalem Hammed, Nolan Chatron, Jean Valéry Debaux, Etienne Benoit, Virginie Lattard
BACKGROUND: After its initial use, resistance to difenacoum has been detected rapidly in rats in north-east Hampshire and north-west Berkshire in England. Resistance to difenacoum has been reported to be stronger in rats from Berkshire than rats from Hampshire. Surprisingly, after the discovery of the Vkorc1 gene, rats from Berkshire and Hampshire were all shown to be homozygous for the L120Q mutation in the Vkorc1. RESULTS: This study aims to evaluate the resistance of Berkshire rats to confirm their extreme resistance and determine mechanisms supporting this resistance...
November 20, 2017: Pest Management Science
https://www.readbyqxmd.com/read/29055218/cyp2c9-and-vkorc1-in-therapeutic-dosing-and-safety-of-acenocoumarol-treatment-implication-for-clinical-practice-in-hungary
#12
Reka Varnai, Csilla Sipeky, Lajos Nagy, Sandor Balogh, Bela Melegh
The purpose of this work was to investigate the contribution of CYP2C9 and VKORC1 to acenocoumarol (AC) dose variability, bleeding events in Hungary. The study recruited 117 patients on long-term AC therapy (INR 2-3), and 510 healthy individuals to model the findings. Patients were genotyped for alleles proved to affect lower AC overdose CYP2C9*2, CYP2C9*3, VKORC1*2. Additionally, we tested VKORC1*3, VKORC1*4 to examine their effect in patients with higher AC requirements. Most impact on dose reduction is accountable for CYP2C9*2/*3 (59%) and for VKORC1*2/*2 (45...
October 8, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29054760/polymorphisms-of-vitamin-k-related-genes-ephx1-and-vkorc1l1-and-stable-warfarin-doses
#13
Jee-Eun Chung, Kyung Eun Lee, Byung Chul Chang, Hye Sun Gwak
The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements...
October 17, 2017: Gene
https://www.readbyqxmd.com/read/28973620/effect-of-genotype-guided-warfarin-dosing-on-clinical-events-and-anticoagulation-control-among-patients-undergoing-hip-or-knee-arthroplasty-the-gift-randomized-clinical-trial
#14
RANDOMIZED CONTROLLED TRIAL
Brian F Gage, Anne R Bass, Hannah Lin, Scott C Woller, Scott M Stevens, Noor Al-Hammadi, Juan Li, Tomás Rodríguez, J Philip Miller, Gwendolyn A McMillin, Robert C Pendleton, Amir K Jaffer, Cristi R King, Brandi DeVore Whipple, Rhonda Porche-Sorbet, Lynnae Napoli, Kerri Merritt, Anna M Thompson, Gina Hyun, Jeffrey L Anderson, Wesley Hollomon, Robert L Barrack, Ryan M Nunley, Gerard Moskowitz, Victor Dávila-Román, Charles S Eby
Importance: Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. Objective: To determine whether genotype-guided dosing improves the safety of warfarin initiation. Design, Setting, and Patients: The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers...
September 26, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28889200/prevalence-of-common-hereditary-risk-factors-for-thrombophilia-in-somalia-and-identification-of-a-novel-gln544arg-mutation-in-coagulation-factor-v
#15
Abshir Ali Abdi, Abdimajid Osman
Thrombophilia, commonly manifested as venous thromboembolism (VTE), is a worldwide concern but little is known on its genetic epidemiology in many parts of the globe particularly in the developing countries. Here we employed TaqMan genotyping and pyrosequencing to evaluate the prevalence of known common nucleotide polymorphisms associated with thrombophilia in a Somali population in the Puntland region of Somalia. We also employed next generation sequencing (NGS) to investigate other genetic variants in a Somali patient with deep venous thrombosis (DVT)...
November 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28867752/genotyping-of-cyp2c9-and-vkorc1-polymorphisms-predicts-south-indian-patients-with-deep-vein-thrombosis-as-fast-metabolizers-of-warfarin-acenocoumarin
#16
Ganesan Arunkumar, Durairajpandian Vishnuprabu, Bitt Nupur, Thiruvengadam Vidyasagaran, Avaniyapuram Kannan Murugan, Arasambattu Kannan Munirajan
Deep vein thrombosis (DVT) is a life-threatening disease. Warfarin and acenocoumarol are anticoagulants used to treat DVT and vary among individuals in terms of treatment response/toxicity. Single nucleotide polymorphisms (SNPs) in CYP2C9 and VKORC1 play a role in the pharmacokinetics and dynamics of warfarin and acenocoumarol and they determine the efficacy of treatment by controlling drug clearance in treated individuals. The aim of the current study was to genotype the critical SNPs of CYP2C9 and VKORC1 genes in a south Indian population in order to understand the metabolizer phenotype of patients with DVT...
2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28834238/long-term-outcomes-of-elderly-patients-with-cyp2c9-and-vkorc1-variants-treated-with-vitamin-k-antagonists
#17
M Nagler, A Angelillo-Scherrer, M Méan, A Limacher, C Abbal, M Righini, J H Beer, J Osterwalder, B Frauchiger, M Aschwanden, C M Matter, N Kucher, J Cornuz, M Banyai, M Husmann, D Staub, L Mazzolai, O Hugli, N Rodondi, D Aujesky
Essentials The long-term effects of VKORC1 and CYP2C9 variants on clinical outcomes remains unclear. We followed 774 patients ≥65 years with venous thromboembolism for a median duration of 30 months. Patients with CYP2C9 variants are at increased risk of death and non-major bleeding. Patients with genetic variants have a slightly lower anticoagulation quality only. SUMMARY: Background The long-term effect of polymorphisms of the vitamin K-epoxide reductase (VKORC1) and the cytochrome P450 enzyme gene (CYP2C9) on clinical outcomes remains unclear...
November 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28817838/pharmacogenetic-determinants-of-outcomes-on-triplet-hepatic-artery-infusion-and-intravenous-cetuximab-for-liver-metastases-from-colorectal-cancer-european-trial-optiliv-nct00852228
#18
Francis Lévi, Abdoulaye Karaboué, Raphaël Saffroy, Christophe Desterke, Valerie Boige, Denis Smith, Mohamed Hebbar, Pasquale Innominato, Julien Taieb, Carlos Carvalho, Rosine Guimbaud, Christian Focan, Mohamed Bouchahda, René Adam, Michel Ducreux, Gérard Milano, Antoinette Lemoine
BACKGROUND: The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes. METHODS: Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes...
September 26, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28689179/genetics-and-clinical-response-to-warfarin-and-edoxaban-in-patients-with-venous-thromboembolism
#19
RANDOMIZED CONTROLLED TRIAL
Alexander G Vandell, Joseph Walker, Karen S Brown, George Zhang, Min Lin, Michael A Grosso, Michele F Mercuri
OBJECTIVE: The aim of this study was to investigate whether genetic variants can identify patients with venous thromboembolism (VTE) at an increased risk of bleeding with warfarin. METHODS: Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity types (normal, sensitive and highly sensitive) based on their genotypes...
November 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28685643/clinical-effect-of-cyp2c9-5-6-genotype-on-a-patient-s-warfarin-dose-requirement
#20
Alison L H Quinn, Ina Liko, James C Lee
We describe a 38-year-old African-American female treated with warfarin for acute bilateral pulmonary emboli who is a carrier of two rare CYP2C9 variant alleles, *5 and *6, along with VKORC1 -1639GG and CYP4F2 433Val/Val genotypes. Warfarin was dosed according to the hospital's Personalized Medicine Program recommendations of 5-6 mg/day for the first 6 days, and reduced to 2.5 mg/day starting on day 8 and continued for the following 3 weeks. This case sheds further light on the cumulative clinical impact of the CYP2C9 variant alleles, *5 and *6, on warfarin dose requirements and practical considerations for warfarin genotyping in a racially and ethnically diverse population...
July 7, 2017: Pharmacogenomics
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