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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
#1
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...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28689179/genetics-and-clinical-response-to-warfarin-and-edoxaban-in-patients-with-venous-thromboembolism
#2
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/28685643/clinical-effect-of-cyp2c9-5-6-genotype-on-a-patient-s-warfarin-dose-requirement
#3
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
https://www.readbyqxmd.com/read/28649054/effect-of-vkorc1-and-cyp2c9-polymorphisms-on-warfarin-dose-requirement-in-bangladeshi-population
#4
Zahid Sadek Chowdhury, Farah Shahjin, Farhana Akter, Maizbhauddin Ahmed, Mohammad Safiqul Islam, Muhammad Shahdaat Bin Sayeed, Reazul Islam, Abul Hasnat
Warfarin, an oral anticoagulant is one of the most widely prescribed drugs in modern medicine. Large inter-individuals variability due to age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes make the management of warfarin therapy challenging and yet no study has been conducted on the Bangladeshi population. The aim of the study was to identify the role of VKORC1 and CYP2C9 polymorphisms in Bangladeshi population in dose requirement of warfarin. We studied 87 heart valve replacement patients who were prescribed warfarin for minimum of 6 months with a target International normalized ratio of 2...
March 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28638342/warfarin-anticoagulation-therapy-in-caribbean-hispanics-of-puerto-rico-a-candidate-gene-association-study
#5
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/28626479/the-allele-frequency-of-cyp2c9-and-vkorc1-in-the-southern-khorasan-population
#6
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
#7
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/28608988/dosing-algorithms-for-vitamin-k-antagonists-across-vkorc1-and-cyp2c9-genotypes-comment
#8
LETTER
T Gaikwad, K Ghosh, S Shetty
No abstract text is available yet for this article.
June 13, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28595918/studies-on-bromadiolone-resistance-in-rattus-rattus-populations-from-punjab-india
#9
Nancy Garg, Neena Singla, Vikas Jindal, Bhupinder K Babbar
There are several reports on development of resistance to bromadiolone in different species of rodents around the globe, however, there is no such report involving systematic study from India. Hence, present study was carried out to investigate current status of bromadiolone resistance in house rat (Rattus rattus; n=154) collected from different poultry farms (n=8) based on feeding test, blood clotting response (BCR) test and molecular characterization of VKORC1 gene. Based on feeding test and BCR test, 28% rats were suspected to be resistant...
June 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28592190/genetic-variants-associated-with-warfarin-dosage-in-kuwaiti-population
#10
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/28550460/the-impact-of-non-genetic-and-genetic-factors-on-a-stable-warfarin-dose-in-thai-patients
#11
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/28546997/pharmacogenomic-findings-from-clinical-whole-exome-sequencing-of-diagnostic-odyssey-patients
#12
Margot A Cousin, Eric T Matey, Patrick R Blackburn, Nicole J Boczek, Tammy M McAllister, Teresa M Kruisselbrink, Dusica Babovic-Vuksanovic, Konstantinos N Lazaridis, Eric W Klee
BACKGROUND: We characterized the pharmacogenomics (PGx) results received by diagnostic odyssey patients as secondary findings during clinical whole exome sequencing (WES) testing as a part of their care in Mayo Clinic's Individualized Medicine Clinic to determine the potential benefits and limitations to this cohort. METHODS: WES results on 94 patients included a subset of PGx variants in CYP2C19,CYP2C9, and VKORC1 if identified in the patient. Demographic, phenotypic, and medication usage information was abstracted from patient medical data...
May 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28502675/genotype-guided-dosing-of-warfarin-through-modeling-and-simulation
#13
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/28479094/integrating-genotypes-in-the-same-tt2r2-score-for-the-prediction-of-anticoagulation-control-in-chinese-patients-with-atrial-fibrillation-on-warfarin
#14
Jia Liu, Nina Wang, Liuan Qin, Jun Liu, Shaozhi Xi, Xuyun Wang, Xiaoqi Li, Yuxiao Zhang, Tong Yin
INTRODUCTION: The SAMe-TT2R2 score has been proposed to predict whether patients with atrial fibrillation (AF) would be well anti-coagulated with warfarin or not. However, it might over-estimate the number of patients under suboptimal warfarin treatment in non-Caucasians. This study was designed to modify the SAMe-TT2R2 score with genotypes and validate it in Chinese AF patients treated with warfarin. MATERIAL AND METHODS: Consented Chinese-Han patients (n=510) with AF under the treatment of warfarin for at least 3months were randomly divided into a derivation (n=310) and a validation cohort (n=200)...
April 29, 2017: International Journal of Cardiology
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
#15
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/28428867/adaptative-evolution-of-the-vkorc1-gene-in-mus-musculus-domesticus-is-influenced-by-the-selective-pressure-of-anticoagulant-rodenticides
#16
Joffrey Goulois, Véronique Lambert, Lionel Legros, Etienne Benoit, Virginie Lattard
Anticoagulant rodenticides are commonly used to control rodent pests worldwide. They specifically inhibit the vitamin K epoxide reductase (VKORC1), which is an enzyme encoded by the Vkorc1 gene, involved in the recycling of vitamin K. Therefore, they prevent blood clotting. Numerous mutations of Vkorc1 gene were reported in rodents, and some are involved in the resistant to rodenticides phenotype. Two hundred and sixty-six mice tails were received from 65 different locations in France. Coding sequences of Vkorc1 gene were sequenced in order to detect mutations...
April 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28412319/genetic-and-non-genetic-factors-affecting-the-quality-of-anticoagulation-control-and-vascular-events-in-atrial-fibrillation
#17
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
#18
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/28401802/the-impact-of-gene-polymorphisms-on-anticoagulation-control-with-warfarin
#19
Hai He Jiang, Jia Liu, Yi Chen Wang, Hui Ming Ye, Xi Li, Ya Xing Zhou, Wei Zhang, Lian Sheng Wang
Differences in warfarin maintenance dosages based on the presence of polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through dosage adjustment according to routine guidelines. Little is known about whether routine therapy could provide consensus anticoagulation control for patients with different genotypes. This study was carried out to compare anticoagulant control in patients with different genotypes. Six hundred seventy patients using warfarin according to Chinese guidelines were enrolled...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28388432/large-diverse-population-cohorts-of-hipscs-and-derived-hepatocyte-like-cells-reveal-functional-genetic-variation-at-blood-lipid-associated-loci
#20
Evanthia E Pashos, YoSon Park, Xiao Wang, Avanthi Raghavan, Wenli Yang, Deepti Abbey, Derek T Peters, Juan Arbelaez, Mayda Hernandez, Nicolas Kuperwasser, Wenjun Li, Zhaorui Lian, Ying Liu, Wenjian Lv, Stacey L Lytle-Gabbin, Dawn H Marchadier, Peter Rogov, Jianting Shi, Katherine J Slovik, Ioannis M Stylianou, Li Wang, Ruilan Yan, Xiaolan Zhang, Sekar Kathiresan, Stephen A Duncan, Tarjei S Mikkelsen, Edward E Morrisey, Daniel J Rader, Christopher D Brown, Kiran Musunuru
Genome-wide association studies have struggled to identify functional genes and variants underlying complex phenotypes. We recruited a multi-ethnic cohort of healthy volunteers (n = 91) and used their tissue to generate induced pluripotent stem cells (iPSCs) and hepatocyte-like cells (HLCs) for genome-wide mapping of expression quantitative trait loci (eQTLs) and allele-specific expression (ASE). We identified many eQTL genes (eGenes) not observed in the comparably sized Genotype-Tissue Expression project's human liver cohort (n = 96)...
April 6, 2017: Cell Stem Cell
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