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warfarin genetic

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https://www.readbyqxmd.com/read/29156869/impact-of-ggcx-polymorphisms-on-warfarin-dose-requirements-in-atrial-fibrillation-patients
#1
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/29095091/an-assessment-of-the-impact-of-pharmacogenomics-on-health-disparities-a-systematic-literature-review
#2
Antony Martin, Jennifer Downing, Michelle Maden, Nigel Fleeman, Ana Alfirevic, Alan Haycox, Munir Pirmohamed
This review assessed evidence of disparities in benefits of pharmacogenomics related to 'model performance' in subgroups of patients and studies which reported impact on health inequalities. 'Model performance' refers to the ability of algorithms including clinical, environmental and genetic information to guide treatment. A total of 4978 abstracts were screened by one reviewer and 30% (1494) were double screened by a second independent reviewer, after which data extraction was performed. Additional forward and backward citation searching of reference lists was conducted...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29054760/polymorphisms-of-vitamin-k-related-genes-ephx1-and-vkorc1l1-and-stable-warfarin-doses
#3
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/29040422/pharmacogenetics-a-general-review-on-progress-to-date
#4
Ann K Daly
Background: Pharmacogenetics is not a new subject area but its relevance to drug prescribing has become clearer in recent years due to developments in gene cloning and DNA genotyping and sequencing. Sources of data: There is a very extensive published literature concerned with a variety of different genes and drugs. Areas of agreement: There is general agreement that pharmacogenetic testing is essential for the safe use of drugs such as the thiopurines and abacavir...
October 11, 2017: British Medical Bulletin
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
#5
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/28949423/influence-of-kidney-transplant-status-on-warfarin-dose-anticoagulation-control-and-risk-of-hemorrhage
#6
Megan V Yanik, Marguerite R Irvin, T Mark Beasley, Pamala A Jacobson, Bruce A Julian, Nita A Limdi
STUDY DESIGN: To assess whether warfarin dose requirement, anticoagulation control, and risk of hemorrhage differ in kidney transplant recipients (KTRs) compared with patients without kidney transplants (non-KTRs). DESIGN: Analysis of data from the Warfarin Pharmacogenetics Cohort, a prospective cohort of first-time warfarin users followed at two anticoagulation clinics. SETTING: Two outpatient anticoagulation clinics at two large, academic, tertiary care hospitals...
November 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28933798/pharmacokinetics-of-tecarfarin-and-warfarin-in-patients-with-severe-chronic-kidney-disease
#7
Mark Midei, Detlef Albrecht, Mintu P Turakhia, Daniel Ries, Thomas Marbury, William Smith, Debbie Dillon, Peter G Milner, Mark G Midei
Chronic kidney disease (CKD) complicates warfarin anticoagulation partially through its effect on CYP2C9 activity. Tecarfarin, a novel vitamin K antagonist, is not metabolized by CYP2C9. To evaluate the effect of CKD on their metabolism, we measured PK parameters of warfarin and tecarfarin in subjects with and without CKD. CKD subjects with estimated glomerular filtration rate < 30 mL/min not on dialysis (n = 13) were matched to healthy volunteers (HVs) (n = 10). Each subject was randomized to either warfarin 10 mg or tecarfarin 30 mg and was later crossed over to the other drug...
September 21, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28931618/predicting-major-bleeding-in-ischemic-stroke-patients-with-atrial-fibrillation
#8
RANDOMIZED CONTROLLED TRIAL
Nina A Hilkens, Ale Algra, Jacoba P Greving
BACKGROUND AND PURPOSE: Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories. METHODS: We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy)...
November 2017: Stroke; a Journal of Cerebral Circulation
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
#9
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/28872889/association-between-the-lower-extremity-deep-venous-thrombosis-the-warfarin-maintenance-dose-and-cyp2c9-3-cyp2d6-10-and-cyp3a5-3-genetic-polymorphisms-a-case-control-study
#10
Shang Ju, Yu Gao, Xin Cao, Xiao-Fu Zhang, Cheng-Cheng Yan, Feng-Tong Liu
OBJECTIVE: This study explored the association between the CYP2C9*3/CYP2D6*10/CYP3A5*3 genetic polymorphisms with lower extremity deep venous thrombosis (LEDVT) and the warfarin maintenance dose. METHODS: Five hundred thirty-six patients who were pathologically diagnosed with LEDVT after surgery were included in the LEDVT group. At the same time, 540 patients without LEDVT who underwent surgery were recruited as the control group. Patients were given warfarin at an initial dose of 2...
September 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28810573/warfarin-induced-life-threatening-bleeding-associated-with-a-cyp3a4-loss-of-function-mutation-in-an-acute-limb-ischemia-patient-case-report-and-review-of-the-literature
#11
Xiao-Wei Ma, Chang-Ning Hao, Zhi-Chun Gu, Meng Ye, Min Li, Lan Zhang
Patients with acute limb ischemia, deep venous thrombosis and pulmonary artery embolism may be treated with warfarin. The dose-response interaction of warfarin is associated with numerous factors, depending on which an uncommon life-threatening bleeding may occur. The present case study reported on a patient with acute limb ischemia and a history of warfarin-induced bleeding ten years previously and who again developed life threatening bleeding associated with warfarin treatment and received vascular surgery...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28806200/quality-of-anticoagulation-control-and-hemorrhage-risk-among-african-american-and-european-american-warfarin-users
#12
Nita A Limdi, Todd M Brown, Aditi Shendre, Nianjun Liu, Charles E Hill, Timothy M Beasley
OBJECTIVE: We evaluated whether percent time in target range (PTTR), risk of over-anticoagulation [international normalized ratio (INR)>4], and risk of hemorrhage differ by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on the risk of hemorrhage by race. PARTICIPANTS AND METHODS: Among 1326 warfarin users, PTTR was calculated as the percentage of interpolated INR values within the target range of 2.0-3.0. PTTR was also categorized as poor (PTTR<60%), good (60≤PTTR<70%), or excellent (PTTR≥70%) anticoagulation control...
October 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28792790/recent-developments-and-future-directions-for-the-use-of-pharmacogenomics-in-cardiovascular-disease-treatments
#13
REVIEW
Elliot Berinstein, Andrew Levy
Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from the patient's genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs. Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28689179/genetics-and-clinical-response-to-warfarin-and-edoxaban-in-patients-with-venous-thromboembolism
#14
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/28689108/multi-objective-feature-selection-for-warfarin-dose-prediction
#15
Mohammad Karim Sohrabi, Alireza Tajik
With increasing the application of decision support systems in various fields, using such systems in different aspects of medical science has been growing. Drug's dose prediction is one of the most important issues which can be improved using decision support systems. In this paper, a new multi-objective feature approach has been proposed to support warfarin dose prediction decision. Warfarin is an anticoagulant normally used in the prevention of the formation of clots. This research was conducted on 553 patients during 2013-2015 who were candidates for using warfarin and their INR was in the target range...
June 28, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28686080/influence-of-common-and-rare-genetic-variation-on-warfarin-dose-among-african-americans-and-european-americans-using-the-exome-array
#16
Nianjun Liu, Marguerite R Irvin, Degui Zhi, Amit Patki, T Mark Beasley, Deborah A Nickerson, Charles E Hill, Jinbo Chen, Stephen E Kimmel, Nita A Limdi
AIM: We conducted a genome-wide association study using the Illumina Exome Array to identify coding SNPs that may explain additional warfarin dose variability. PATIENTS & METHODS: Analysis was performed after adjustment for clinical variables and genetic factors known to influence warfarin dose among 1680 warfarin users (838 European-Americans and 842 African-Americans). Replication was performed in an independent sample. RESULTS: We confirmed the influence of known genetic variants on warfarin dose variability...
July 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28646384/lipophilicity-influences-drug-binding-to-%C3%AE-1-acid-glycoprotein-f1-s-variants-but-not-to-the-a-variant
#17
Kazuhiko Hanada
OBJECTIVE: Human α1-acid glycoprotein has genetic variants, the F1, S, and A variants, which can be separated isoelectrophoretically. These variants show differences in their affinity of binding to several drugs. In this study, we investigated the factors determining drug binding to these α1-acid glycoprotein genetic variants using disopyramide, warfarin, and tamsulosin as marker compounds. METHODS: Binding of the marker drugs to human α1-acid glycoprotein was determined by ultra-filtration in the presence or absence of various other drugs...
September 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28638342/warfarin-anticoagulation-therapy-in-caribbean-hispanics-of-puerto-rico-a-candidate-gene-association-study
#18
Karla Claudio-Campos, Aurora Labastida, Alga Ramos, Andrea Gaedigk, Jessicca Renta-Torres, Dariana Padilla, Giselle Rivera-Miranda, Stuart A Scott, Gualberto Ruaño, Carmen L Cadilla, Jorge Duconge-Soler
Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28634997/working-toward-precision-medicine-predicting-phenotypes-from-exomes-in-the-critical-assessment-of-genome-interpretation-cagi-challenges
#19
Roxana Daneshjou, Yanran Wang, Yana Bromberg, Samuele Bovo, Pier L Martelli, Giulia Babbi, Pietro Di Lena, Rita Casadio, Matthew Edwards, David Gifford, David T Jones, Laksshman Sundaram, Rajendra Rana Bhat, Xiaolin Li, Lipika R Pal, Kunal Kundu, Yizhou Yin, John Moult, Yuxiang Jiang, Vikas Pejaver, Kymberleigh A Pagel, Biao Li, Sean D Mooney, Predrag Radivojac, Sohela Shah, Marco Carraro, Alessandra Gasparini, Emanuela Leonardi, Manuel Giollo, Carlo Ferrari, Silvio C E Tosatto, Eran Bachar, Johnathan R Azaria, Yanay Ofran, Ron Unger, Abhishek Niroula, Mauno Vihinen, Billy Chang, Maggie H Wang, Andre Franke, Britt-Sabina Petersen, Mehdi Pirooznia, Peter Zandi, Richard McCombie, James B Potash, Russ B Altman, Teri E Klein, Roger A Hoskins, Susanna Repo, Steven E Brenner, Alexander A Morgan
Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge...
September 2017: Human Mutation
https://www.readbyqxmd.com/read/28626479/the-allele-frequency-of-cyp2c9-and-vkorc1-in-the-southern-khorasan-population
#20
Fariba Emadian Razavi, Asghar Zarban, Fatemeh Hajipoor, Mohsen Naseri
The genetic factors are determinants in required dosage changes of warfarin among which are polymorphisms of CYP2C9 and VKORC1 genes. The present study aimed to determine the allele and genotype frequency of CYP2C9 and VKORC1 genes in Birjand population. This study was conducted on 120 individuals who referred to Imam Reza and Vali-Asr hospitals for PT/INR test. After extracting the genomic DNA, the considered sequences were amplified by PCR, and restriction fragment length polymorphism analysis was done by AvaII and KpnI enzymes to determine allele polymorphisms...
June 2017: Research in Pharmaceutical Sciences
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