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https://www.readbyqxmd.com/read/28550460/the-impact-of-non-genetic-and-genetic-factors-on-a-stable-warfarin-dose-in-thai-patients
#1
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...
May 26, 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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28412319/genetic-and-non-genetic-factors-affecting-the-quality-of-anticoagulation-control-and-vascular-events-in-atrial-fibrillation
#6
Yun Kyung Park, Mi Ji Lee, Jae Ha Kim, Jin Soo Lee, Rae Woong Park, Gyeong-Moon Kim, Chin-Sang Chung, Kwang Ho Lee, June Soo Kim, Soo-Youn Lee, Oh Young Bang
BACKGROUND: Warfarin has a narrow therapeutic window. We hypothesized that genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1) would show stronger associations than modifiable factors with the quality of anticoagulation control and risks for thromboembolism and hemorrhage. METHODS: In this retrospective cohort analysis, clinical and genetic data were collected from 380 patients with atrial fibrillation (AF) who were followed for an average observation period of 4 years...
April 12, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28408837/polymorphisms-of-vkorc1-and-cyp2c9-are-associated-with-warfarin-sensitivity-in-chinese-population
#7
LiQun Jia, Zanxin Wang, Jianlong Men, Heng Cai, Minxin Wei
OBJECTIVE: Warfarin is a commonly prescribed anticoagulant for prevention of thromboembolic events. Wide inter-individual dose variation, narrow therapeutic range and risk of serious bleeding result in difficulties in achieving the therapeutic effect. The present study was designed to clarify the real biological significance of the polymorphisms of VKORC1 and cytochrome P450 2C9 (CYP2C9) in warfarin metabolism. METHODS: A total of 214 patients with warfarin anticoagulant therapy were selected...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28268853/optimal-decision-support-rules-improve-personalize-warfarin-treatment-outcomes
#8
Chih-Lin Chi, Kourosh Ravvaz, John Weissert, Peter J Tonellato
We tested optimization-based approaches to generate decision support rules used to improve personalized warfarin treatment based on clinical and genetic characteristics. Our approach simulated warfarin treatment outcomes using five existing treatment plans for clinical avatars (virtual patients). We used individual clinical avatar Time-in-Therapeutic-Range to represent the two-sided adverse risk to bleeding (over dosed - above therapeutic range) and thrombosis (under dosed - below therapeutic range) and as the objective function in the optimization to minimize overall risk...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28262345/influence-of-nr3c1-and-vdr-polymorphisms-on-stable-warfarin-dose-in-patients-with-mechanical-cardiac-valves
#9
Kyung Eun Lee, Jee Eun Chung, Boram Yi, Yoon Jeong Cho, Hyun Jeong Kim, Gwan Yung Lee, Joo Hee Kim, Byung Chul Chang, Hye Sun Gwak
OBJECTIVES: The aim of this study was to evaluate the associations between polymorphisms of VKORC1, CYP2C9, CYP4F2, NR3C1 and VDR genes and stable warfarin doses in Korean patients with mechanical heart valves. METHODS: Seventeen single-nucleotide polymorphisms (SNPs) in 204 patients with stable warfarin dose were analyzed: VKORC1 (rs9934438), CYP2C9 (rs1057910), CYP4F2 (rs2108622), NR3C1 (rs41423247, rs1800445, rs56149945, rs10052957, rs6198, rs33388, rs6196, and rs244465), and VDR (rs1544410, rs11568820, rs731236, rs757343, rs7975232, and rs2228570)...
February 24, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28259826/medical-management-of-extensive-arterial-thromboembolism-in-a-patient-with-essential-thrombocythemia-and-warfarin-failure
#10
Aisha K Ahmed, Alicia Youssef, Nedaa Skeik
Chronic myeloproliferative disorders share a stem cell-derived clonal myeloproliferation. This group of disorders include essential thrombocythemia (ET), polycythemia vera (PV), chronic myeloid leukemia, and primary myelofibrosis (PMF), with the respective features of thrombocytosis, erythrocytosis, and bone marrow fibrosis. These disorders can be associated with genetic mutations affecting protein tyrosine kinases, resulting in different configurations of abnormal signal transduction. The Janus tyrosine kinase 2 mutation can be used as a key diagnostic tool for diagnosing MPDs, specifically, ET, PV, and PMF...
March 1, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28227051/optimal-decision-support-rules-improve-personalize-warfarin-treatment-outcomes
#11
Chih-Lin Chi, Kourosh Ravvaz, John Weissert, Peter J Tonellato, Chih-Lin Chi, Kourosh Ravvaz, John Weissert, Peter J Tonellato, Chih-Lin Chi, Kourosh Ravvaz, John Weissert, Peter J Tonellato
We tested optimization-based approaches to generate decision support rules used to improve personalized warfarin treatment based on clinical and genetic characteristics. Our approach simulated warfarin treatment outcomes using five existing treatment plans for clinical avatars (virtual patients). We used individual clinical avatar Time-in-Therapeutic-Range to represent the two-sided adverse risk to bleeding (over dosed - above therapeutic range) and thrombosis (under dosed - below therapeutic range) and as the objective function in the optimization to minimize overall risk...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28224948/predictors-of-warfarin-dose-requirements-in-south-african-patients-attending-an-anticoagulation-clinic
#12
Elise Schapkaitz, Johanna Sithole
INTRODUCTION: Warfarin is the most common oral anticoagulant for the treatment and prevention of thromboembolic disease. However, it has a wide interpatient variability in dose requirements due to various genetic and clinical factors. MATERIALS AND METHODS: This study investigated the effect of clinical and genetic factors on the variability of warfarin dose requirements in 147 South African patients (81 white and 66 black). The study was performed at a University Hospital Anticoagulation Clinic managed by nursing sisters at the Charlotte Maxeke Johannesburg Academic Hospital...
March 2017: Journal of Vascular Nursing: Official Publication of the Society for Peripheral Vascular Nursing
https://www.readbyqxmd.com/read/28135054/integrated-analysis-of-genetic-variation-and-gene-expression-reveals-novel-variant-for-increased-warfarin-dose-requirement-in-african-americans
#13
W Hernandez, E R Gamazon, K Aquino-Michaels, E Smithberger, T J O'Brien, A F Harralson, M Tuck, A Barbour, L H Cavallari, M A Perera
Essentials Genetic variants controlling gene regulation have not been explored in pharmacogenomics. We tested liver expression quantitative trait loci for association with warfarin dose response. A novel predictor for increased warfarin dose response in African Americans was identified. Precision medicine must take into account population-specific variation in gene regulation. SUMMARY: Background Warfarin is commonly used to control and prevent thromboembolic disorders. However, because of warfarin's complex dose-requirement relationship, safe and effective use is challenging...
April 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079798/clinical-and-genetic-factors-associated-with-warfarin-maintenance-dose-in-northern-chinese-patients-with-mechanical-heart-valve-replacement
#14
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
#15
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...
April 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
#16
J Holm, J D Lindh, M L Andersson, B Mannheimer
Essentials Data on the effect of introducing amiodarone in patients already using warfarin regime are scarce. Information on 754 patients was extracted from three nationwide registers in Sweden. With amiodaron, 37% of patients had an international normalized ratio (INR) over 3.0 To avoid bleeding, the initiation of amiodarone should be accompanied by closer INR monitoring. SUMMARY: Background Data indicate that the interaction between warfarin and amiodarone results in an increased warfarin effect...
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
#17
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
#18
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
#19
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
#20
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
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