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warfarin genetic

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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
#1
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)...
September 9, 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
#2
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
#3
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
#4
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...
August 11, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28792790/recent-developments-and-future-directions-for-the-use-of-pharmacogenomics-in-cardiovascular-disease-treatments
#5
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...
August 20, 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
#6
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...
July 8, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28689108/multi-objective-feature-selection-for-warfarin-dose-prediction
#7
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
#8
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
#9
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...
June 23, 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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28620303/effect-of-genetic-variability-in-the-cyp4f2-cyp4f11-and-cyp4f12-genes-on-liver-mrna-levels-and-warfarin-response
#13
J E Zhang, Kathrin Klein, Andrea L Jorgensen, Ben Francis, Ana Alfirevic, Stephane Bourgeois, Panagiotis Deloukas, Ulrich M Zanger, Munir Pirmohamed
Genetic polymorphisms in the gene encoding cytochrome P450 (CYP) 4F2, a vitamin K oxidase, affect stable warfarin dose requirements and time to therapeutic INR. CYP4F2 is part of the CYP4F gene cluster, which is highly polymorphic and exhibits a high degree of linkage disequilibrium, making it difficult to define causal variants. Our objective was to examine the effect of genetic variability in the CYP4F gene cluster on expression of the individual CYP4F genes and warfarin response. mRNA levels of the CYP4F gene cluster were quantified in human liver samples (n = 149) obtained from a well-characterized liver bank and fine mapping of the CYP4F gene cluster encompassing CYP4F2, CYP4F11, and CYP4F12 was performed...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28592190/genetic-variants-associated-with-warfarin-dosage-in-kuwaiti-population
#14
Sumi Elsa John, Dinu Antony, Muthukrishnan Eaaswarkhanth, Prashantha Hebbar, Fadi Alkayal, Jaakko Tuomilehto, Osama Alsmadi, Thangavel Alphonse Thanaraj
Assessing the distinct prevalence or absence of genetic variants associated with differential response to the anticoagulant medication of warfarin in different population groups is actively pursued by pharmacogenomics community. Populations from Arabian Peninsula are underrepresented in such studies. By way of examining exome- and genome-wide genotype data from 1395 Arab individuals in Kuwait, we report distinct occurrence of warfarin response-related variants rs12460590_A/CYP2A7, rs2108622_T/CYP4F2, rs2884737_C/VKORC1 and distinct absence of rs11150606_C/PRSS53 in Kuwaiti population...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28571507/the-genetic-basis-of-antiplatelet-and-anticoagulant-therapy-a-pharmacogenetic-review-of-newer-antiplatelets-clopidogrel-prasugrel-and-ticagrelor-and-anticoagulants-dabigatran-rivaroxaban-apixaban-and-edoxaban
#15
REVIEW
Cormac T O'connor, Thomas J Kiernan, Bryan P Yan
The study of pharmacogenomics presents the possibility of individualised optimisation of drug therapy tailored to each patients' unique physiological traits. Both antiplatelet and anticoagulant drugs play a key role in the management of cardiovascular disease. Despite their importance, there is a substantial volume of literature to suggest marked person-to-person variability in their effect. Areas covered: This article reviews the data available for the genetic cause for this inter-patient variability of antiplatelet and anticoagulant drugs...
July 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28550460/the-impact-of-non-genetic-and-genetic-factors-on-a-stable-warfarin-dose-in-thai-patients
#16
Nitsupa Wattanachai, Sutthida Kaewmoongkun, Burabha Pussadhamma, Pattarapong Makarawate, Chaiyasith Wongvipaporn, Songsak Kiatchoosakun, Suda Vannaprasaht, Wichittra Tassaneeyakul
PURPOSE: The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. METHODS: A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays...
August 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28537987/congenital-dysfibrinogenemia-in-a-japanese-family-with-fibrinogen-naples-b%C3%AE-ala68thr-manifesting-as-superior-sagittal-sinus-thrombosis
#17
Satoru Yoshida, Tetsuya Kibe, Risa Matsubara, Shin-Ichiro Koizumi, Kenji Nara, Koji Amano, Nobuo Okumura
: Congenital dysfibrinogenemia refers to the presence of a dysfunctional fibrinogen molecule, typically because of mutations in the fibrinogen gene. About 20% of fibrinogen gene mutations are responsible for thrombosis. Here, we described the case of a 17-year-old Japanese boy, who had a sudden stroke because of superior sagittal sinus thrombosis associated with dysfibrinogenemia. Genetic testing confirmed the presence of homozygous fibrinogen Naples (BβAla68Thr) mutation, which was previously reported as a causative mutation for thrombotic dysfibrinogenemia only in an Italian family...
May 22, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28521079/association-between-cyp4f2-genotype-and-circulating-plasma-vitamin-k-concentration-in-children-on-chronic-warfarin-therapy-possible-long-term-implications-for-bone-development-and-vascular-health
#18
Emmanouela Kampouraki, Peter J Avery, Tina Biss, Farhad Kamali
Vitamin K is essential, for the activation of clotting proteins, as well as the biosynthesis of osteocalcin in bones and the activation of matrix-Gla protein needed in maintaining vasculature health. Cytochrome p450 4F2 (CYP4F2) enzyme is involved in vitamin K catabolism. Genetic polymorphism in CYP4F2 is thus likely to affect vitamin K systemic availability. We show that children on chronic warfarin therapy have low levels of vitamin K and vitamin K levels are linked to CYP4F2 genotype. Long-term low levels of vitamin K, influenced by CYP4F2 genotype, might affect bone development and vascular health in children on chronic warfarin therapy...
May 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28502675/genotype-guided-dosing-of-warfarin-through-modeling-and-simulation
#19
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/28429387/the-association-between-ggcx-mir-133-genetic-polymorphisms-and-warfarin-stable-dosage-in-han-chinese-patients-with-mechanical-heart-valve-replacement
#20
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
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