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Christina Mitropoulou, Vasilios Fragoulakis, Ljiljana B Rakicevic, Mirjana M Novkovic, Athanassios Vozikis, Dragan M Matic, Nebojsa M Antonijevic, Dragica P Radojkovic, Ron H van Schaik, George P Patrinos
INTRODUCTION: Clopidogrel, which is activated by the CYP2C19 enzyme, is among the drugs for which all major regulatory agencies recommend genetic testing to be performed to identify a patient's CYP2C19 genotype in order to determine the optimal antiplatelet therapeutic scheme. The CYP2C19*2 and CYP2C19*3 variants are loss-of-function alleles, leading to abolished CYP2C19 function and thus have the risk of thrombotic events for carriers of these alleles on standard dosages, while the CYP2C19*17 allele results in CYP2C19 hyperactivity...
October 21, 2016: Pharmacogenomics
Cristina Longo, Vasiliki Rahimzadeh, Kieran O'Doherty, Gillian Bartlett
AIM: Primary care physicians will play a central role in the successful implementation of pharmacogenomics (PGx); however, important challenges remain. We explored the perspectives of stakeholders on key challenges of the PGx translation process in primary care using deliberative consultations. METHODS: Primary care physicians, patients and policy-makers attended deliberations, where they discussed four ethical questions raised by PGx research and implementation in the primary care context...
October 21, 2016: Pharmacogenomics
Andrew Kl Goey, Tristan M Sissung, Cody J Peer, William D Figg
The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment...
October 21, 2016: Pharmacogenomics
Matthias Samwald, Hong Xu, Kathrin Blagec, Philip E Empey, Daniel C Malone, Seid Mussa Ahmed, Patrick Ryan, Sebastian Hofer, Richard D Boyce
Pre-emptive pharmacogenomic (PGx) testing of a panel of genes may be easier to implement and more cost-effective than reactive pharmacogenomic testing if a sufficient number of medications are covered by a single test and future medication exposure can be anticipated. We analysed the incidence of exposure of individual patients in the United States to multiple drugs for which pharmacogenomic guidelines are available (PGx drugs) within a selected four-year period (2009-2012) in order to identify and quantify the incidence of pharmacotherapy in a nation-wide patient population that could be impacted by pre-emptive PGx testing based on currently available clinical guidelines...
2016: PloS One
Aharon Nachshon, Hanifa J Abu-Toamih Atamni, Yael Steuerman, Roa'a Sheikh-Hamed, Alexandra Dorman, Richard Mott, Juliane C Dohm, Hans Lehrach, Marc Sultan, Ron Shamir, Sascha Sauer, Heinz Himmelbauer, Fuad A Iraqi, Irit Gat-Viks
A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions...
2016: Frontiers in Genetics
James N Ingle, Fang Xie, Matthew J Ellis, Paul E Goss, Lois E Shepherd, Judith-Anne W Chapman, Bingshu E Chen, Michiaki Kubo, Yoichi Furukawa, Yukihide Momozawa, Vered Stearns, Kathleen I Pritchard, Poulami Barman, Erin E Carlson, Matthew P Goetz, Richard M Weinshilboum, Krishna R Kalari, Liewei Wang
Genetic risks in breast cancer remain only partly understood. Here we report the results of a genome-wide association study of germline DNA from 4,658 women, including 252 women experiencing a breast cancer recurrence, who were entered on the MA.27 adjuvant trial comparing the aromatase inhibitors (AI) anastrozole and exemestane. Single nucleotide polymorphisms (SNP) of top significance were identified in the gene encoding MIR2052HG, a long noncoding RNA of unknown function. Heterozygous or homozygous individuals for variant alleles exhibited a ~40% or ~63% decrease, respectively, in the hazard of breast cancer recurrence relative to homozygous wild-type individuals...
October 10, 2016: Cancer Research
Julian A Michely, Sascha K Manier, Achim T Caspar, Simon D Brandt, Jason Wallach, Hans H Maurer
3-Methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeO-PCPy) are two new psychoactive substances (NPS). The aims of the present study were the elucidation of their metabolic fate in rat and pooled human liver microsomes (pHLM), the identification of the cytochrome P450 (CYP) isoenzymes involved, and the detectability using standard urine screening approaches (SUSA) after intake of common users' doses using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-multi-stage mass spectrometry (LC-MSn), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS)...
October 18, 2016: Current Neuropharmacology
Claudia Maria Hattinger, Elisa Tavanti, Marilù Fanelli, Serena Vella, Piero Picci, Massimo Serra
Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Joseph P Kitzmiller, Eduard B Mikulik, Anees M Dauki, Chandrama Murkherjee, Jasmine A Luzum
Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy...
2016: Pharmacogenomics and Personalized Medicine
Kristin Wiisanen Weitzel, Caitrin W McDonough, Amanda R Elsey, Benjamin Burkley, Larisa H Cavallari, Julie A Johnson
Objective. To evaluate the impact of personal genotyping and a novel educational approach on student attitudes, knowledge, and beliefs regarding pharmacogenomics and genomic medicine. Methods. Two online elective courses (pharmacogenomics and genomic medicine) were offered to student pharmacists at the University of Florida using a flipped-classroom, patient-centered teaching approach. In the pharmacogenomics course, students could be genotyped and apply results to patient cases. Results. Thirty-four and 19 student pharmacists completed the pharmacogenomics and genomic medicine courses, respectively, and 100% of eligible students (n=34) underwent genotyping...
September 25, 2016: American Journal of Pharmaceutical Education
Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
M B Madsen, L J A Kogelman, H N Kadarmideen, H B Rasmussen
Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel the involved genetic components. Moreover, we investigated the potential difference in the genetic interaction networks underlying SSRI treatment response over time. We found four hub genes (ASCC3, PPARGC1B, SCHIP1 and TMTC2) with different connectivity in the initial SSRI treatment period (baseline to week 4) compared with the subsequent period (4-8 weeks after initiation), suggesting that different genetic networks are important at different times during SSRI treatment...
October 18, 2016: Pharmacogenomics Journal
José E Belizário, Beatriz A Sangiuliano, Marcela Perez-Sosa, Jennifer M Neyra, Dayson F Moreira
With multiple omics strategies being applied to several cancer genomics projects, researchers have the opportunity to develop a rational planning of targeted cancer therapy. The investigation of such numerous and diverse pharmacogenomic datasets is a complex task. It requires biological knowledge and skills on a set of tools to accurately predict signaling network and clinical outcomes. Herein, we describe Web-based in silico approaches user friendly for exploring integrative studies on cancer biology and pharmacogenomics...
2016: Frontiers in Pharmacology
Shabbir Ahmed, Zhan Zhou, Jie Zhou, Shu-Qing Chen
The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual's particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pharmacogenomics of phase-I drug metabolizing enzymes and transporters...
October 8, 2016: Genomics, Proteomics & Bioinformatics
Soo Min Han, Joonhee Park, Ji Hyun Lee, Sang Seop Lee, Hyoki Kim, Hyojun Han, Yuhnam Kim, Sojeong Yi, Joo-Youn Cho, In-Jin Jang, Min Goo Lee
Phenotypic differences in drug responses have been associated with known pharmacogenomic loci, but many remain to be characterized. We therefore developed next-generation sequencing (NGS) panels to enable broad and unbiased inspection of genes that are involved in pharmacokinetics (PK) and pharmacodynamics (PD). These panels feature repetitively optimized probes to capture up to 114 PK/PD-related genes with high coverage (99.6%) and accuracy (99.9%). Sequencing of a Korean cohort (n = 376) with the panels enabled profiling of actionable variants as well as rare variants of unknown functional consequences...
October 11, 2016: Clinical Pharmacology and Therapeutics
İbrahim Ömer Barlas, Orhan Sezgin, Collet Dandara, Gözde Türköz, Emre Yengel, Zinhle Cindi, Handan Ankaralı, Semra Şardaş
Pharmacogenomics harnesses the utility of a patient's genome (n = 1) in decisions on which therapeutic drugs and in what amounts should be administered. Often, patients with shared ancestry present with comparable genetic profiles that predict drug response. However, populations are not static, thus, often, population mobility through migration, especially enmasse as is seen for refugees, changes the pharmacogenetic profiles of resultant populations and therefore observed responses to commonly used therapeutic drugs...
October 2016: Omics: a Journal of Integrative Biology
Yanbing Zu, Min-Han Tan, Chee Ren Ee, Jackie Y Ying
A number of human leukocyte antigen (HLA) gene alleles have been found to be genetic risk markers for immunologically mediated drug hypersensitivity. Clinical adoption of HLA pharmacogenomics requires facile and accurate allele screening assays. As HLA genes are highly polymorphic, currently available methods are usually labor-intensive and liable to generate false positives. Herein we report a general strategy for screening HLA alleles with nanoparticle probes. Specific HLA alleles can be identified by gauging three to five sequence variants...
October 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Patrick C M Wong, Loan Vuong, Kevin Liu
Variability in drug responsivity has prompted the development of Personalized Medicine, which has shown great promise in utilizing genotypic information to develop safer and more effective drug regimens for patients. Similarly, individual variability in learning outcomes has puzzled researchers who seek to create optimal learning environments for students. "Personalized Learning" seeks to identify genetic, neural and behavioral predictors of individual differences in learning and aims to use predictors to help create optimal teaching paradigms...
October 5, 2016: Neuropsychologia
David A Khan
Adverse drug reactions (ADRs) are a relatively common cause of morbidity and mortality. Many factors can contribute to ADRs, including genetics. The degree to which genetics contributes to ADRs is not entirely clear and varies by drug, as well as the type of ADR. Pharmacogenetics and, more recently, pharmacogenomics have been applied to the field of ADRs for both predictable ADRs and hypersensitivity drug reactions. Evaluations for glucose-6-phosphate dehydrogenase and thiopurine S-methyltransferase are commonplace clinical tests to reduce hematologic problems associated with drugs, such as dapsone and azathioprine, respectively...
October 2016: Journal of Allergy and Clinical Immunology
Ange C Iliza, Alexis Matteau, Jason R Guertin, Dominic Mitchell, Fiorella Fanton-Aita, Anick Dubois, Marie-Pierre Dubé, Jean-Claude Tardif, Jacques LeLorier
Pharmacogenomics (PGx) tests have the potential of improving the effectiveness of expensive new drugs by predicting the likelihood, for a particular patient, to respond to a treatment. The objective of this study was to develop a pharmacoeconomic model to determine the characteristics and the cost-effectiveness of a hypothetical PGx test, which would identify patients who are most likely to respond to an expensive treatment for chronic heart failure. For this purpose, we chose the example of ivabradine. Our results suggest that the use of a PGx test that could select a subgroup of patients to be treated with an expensive drug has the potential to provide more efficient drug utilization...
October 10, 2016: Pharmacogenomics
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