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Pharmacogenomic

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https://www.readbyqxmd.com/read/29343412/implementing-genome-driven-personalized-cardiology-in-clinical-practice
#1
REVIEW
Ares Pasipoularides
Genomics designates the coordinated investigation of a large number of genes in the context of a biological process or disease. It may be long before we attain comprehensive understanding of the genomics of common complex cardiovascular diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and atherosclerotic heart disease, hypertensive syndromes, and heart failure with preserved/reduced ejection fraction. Nonetheless, as genomics is evolving rapidly, it is constructive to survey now pertinent concepts and breakthroughs...
January 14, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29337087/genetic-polymorphisms-of-pharmacogenomic-vip-variants-in-the-yi-population-from-china
#2
Mengdan Yan, Dianzhen Li, Guige Zhao, Jing Li, Fanglin Niu, Bin Li, Peng Chen, Tianbo Jin
INTRODUCTION: Drug response and target therapeutic dosage are different among individuals. The variability is largely genetically determined. With the development of pharmacogenetics and pharmacogenomics, widespread research have provided us a wealth of information on drug-related genetic polymorphisms, and the very important pharmacogenetic (VIP) variants have been identified for the major populations around the world whereas less is known regarding minorities in China, including the Yi ethnic group...
January 11, 2018: Gene
https://www.readbyqxmd.com/read/29331453/are-privacy-enhancing-technologies-for-genomic-data-ready-for-the-clinic-a-survey-of-medical-experts-of-the-swiss-hiv-cohort-study
#3
Jean-Louis Raisaro, Paul J McLaren, Jacques Fellay, Matthias Cavassini, Catherine Klersy, Jean-Pierre Hubaux
PURPOSE: Protecting patient privacy is a major obstacle for the implementation of genomic-based medicine. Emerging privacy-enhancing technologies can become key enablers for managing sensitive genetic data. We studied physicians' attitude toward this kind of technology in order to derive insights that might foster their future adoption for clinical care. METHODS: We conducted a questionnaire-based survey among 55 physicians of the Swiss HIV Cohort Study who tested the first implementation of a privacy-preserving model for delivering genomic test results...
January 10, 2018: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/29325731/pharmacogenomic-testing-in-child-and-adolescent-psychiatry-an-evidence-based-review
#4
Anna M Wehry, Laura Ramsey, Shane E Dulemba, Sarah A Mossman, Jeffrey R Strawn
Significant advances have been made in the application of pharmacogenomic testing for the treatment of patients with psychiatric disorders. Over the past decade, a number of studies have evaluated the utility of pharmacogenomic testing in pediatric patients with psychiatric disorders. The evidence base for pharmacogenomic testing in youth with depressive and anxiety disorders as well as attention/deficit hyperactivity disorder (ADHD) is reviewed in this article. General pharmacogenomic principles are summarized and functional polymorphisms in P450 enzymes (and associated metabolizer phenotypes), the serotonin transporter promoter polymorphisms, serotonin 2 A receptor genes (e...
January 8, 2018: Current Problems in Pediatric and Adolescent Health Care
https://www.readbyqxmd.com/read/29317847/pharmacogenetic-guidance-individualized-medicine-promotes-enhanced-pain-outcomes
#5
Lisa Lynn Dragic, Erica L Wegrzyn, Michael E Schatman, Jeffrey Fudin
The use of pharmacogenomics has become more prevalent over the past several years in treating many disease states. Several cytochrome P450 enzymes play a role in the metabolism of many pain medications including opioids and antidepressants. Noncytochrome P450 enzymes such as methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) also play a role in the explanation of opioid dosage requirements as well as in response to certain antidepressants. We present the case of a patient with reduced COMT and MTHFR expression treated with leucovorin 10 mg daily for the management of chronic pain...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29316365/developing-pharmacogenomic-reports-insights-from-patients-and-clinicians
#6
Laney K Jones, Alanna Kulchak Rahm, Michael R Gionfriddo, Janet L Williams, Audrey L Fan, Rebecca A Pulk, Eric A Wright, Marc S Williams
Increasingly, for a variety of indications, patients have their genomes sequenced and actionable results returned. A subset of returned results is pharmacogenomic (PGx) variants involved in the metabolism or action of medications. Although the impact of these variants on health is well-documented, little research exists on how to communicate these findings to patients and clinicians. We conducted semistructured interviews with end users to understand how best to communicate PGx results. Overall, patients and clinicians had similar opinions regarding report content, delivery, and application...
January 8, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29315502/a-genome-wide-association-study-identifies-a-candidate-gene-associated-with-atazanavir-exposure-measured-in-hair
#7
Bani Tamraz, Yong Huang, Audrey L French, Seble Kassaye, Kathryn Anastos, Marek J Nowicki, Stephen Gange, Deborah R Gustafson, Peter Bacchetti, Ruth M Greenblatt, Pirro G Hysi, Bradley E Aouizerat
Hair provides a direct measure of long-term exposure of atazanavir (ATV). We report the results of the first genome-wide association study (GWAS) of ATV exposure measured in hair in an observational cohort representative of U.S. women living with HIV; the Women's Interagency HIV Study. Approximately 14.1 million SNPs were analyzed in linear regression-based GWAS, with replication, adjusted for non-genetic predictors collected under conditions of actual use of ATV in 398 participants. Lastly, the PharmGKB database was used to identify pharmacogene associations with ATV exposure...
January 9, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29313952/how-to-consider-rare-genetic-variants-in-personalized-drug-therapy
#8
Volker M Lauschke, Magnus Ingelman-Sundberg
Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME)...
January 5, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29310768/sjs-ten-2017-building-multidisciplinary-networks-to-drive-science-and-translation
#9
REVIEW
Katie D White, Riichiro Abe, Michael Ardern-Jones, Thomas Beachkofsky, Charles Bouchard, Bruce Carleton, James Chodosh, Ricardo Cibotti, Robert Davis, Joshua C Denny, Roni P Dodiuk-Gad, Elizabeth N Ergen, Jennifer L Goldman, James H Holmes, Shuen-Iu Hung, Mario E Lacouture, Rannakoe J Lehloenya, Simon Mallal, Teri A Manolio, Robert G Micheletti, Caroline M Mitchell, Maja Mockenhaupt, David A Ostrov, Rebecca Pavlos, Munir Pirmohamed, Elena Pope, Alec Redwood, Misha Rosenbach, Michael D Rosenblum, Jean-Claude Roujeau, Arturo P Saavedra, Hajirah N Saeed, Jeffery P Struewing, Hirohiko Sueki, Chonlaphat Sukasem, Cynthia Sung, Jason A Trubiano, Jessica Weintraub, Lisa M Wheatley, Kristina B Williams, Brandon Worley, Wen-Hung Chung, Neil H Shear, Elizabeth J Phillips
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening, immunologically mediated, and usually drug-induced disease with a high burden to individuals, their families, and society with an annual incidence of 1 to 5 per 1,000,000. To effect significant reduction in short- and long-term morbidity and mortality, and advance clinical care and research, coordination of multiple medical, surgical, behavioral, and basic scientific disciplines is required. On March 2, 2017, an investigator-driven meeting was held immediately before the American Academy of Dermatology Annual meeting for the central purpose of assembling, for the first time in the United States, clinicians and scientists from multiple disciplines involved in SJS/TEN clinical care and basic science research...
January 2018: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29302224/tobacco-use-disorder-and-treatment-new-challenges-and-opportunities
#10
Douglas Ziedonis, Smita Das, Celine Larkin
Tobacco use remains a global problem, and options for consumers have increased with the development and marketing of e-cigarettes and other new nicotine and tobacco products, such as "heat-not-burn" tobacco and dissolvable tobacco. The increased access to these new products is juxtaposed with expanding public health and clinical intervention options, including mobile technologies and social media. The persistent high rate of tobacco-use disorders among those with psychiatric disorders has gathered increased global attention, including successful approaches to individual treatment and organizational-level interventions...
September 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/29300844/link-synthetic-lethality-to-drug-sensitivity-of-cancer-cells
#11
Ruiping Wang, Yue Han, Zhangxiang Zhao, Fan Yang, Tingting Chen, Wenbin Zhou, Xianlong Wang, Lishuang Qi, Wenyuan Zhao, Zheng Guo, Yunyan Gu
Synthetic lethal (SL) interactions occur when alterations in two genes lead to cell death but alteration in only one of them is not lethal. SL interactions provide a new strategy for molecular-targeted cancer therapy. Currently, there are few drugs targeting SL interactions that entered into clinical trials. Therefore, it is necessary to investigate the link between SL interactions and drug sensitivity of cancer cells systematically for drug development purpose. We identified SL interactions by integrating the high-throughput data from The Cancer Genome Atlas, small hairpin RNA data and genetic interactions of yeast...
December 28, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29288229/genetic-variation-in-cfh-predicts-phenytoin-induced-maculopapular-exanthema-in-european-descent-patients
#12
Mark McCormack, Hongsheng Gui, Andrés Ingason, Doug Speed, Galen E B Wright, Eunice J Zhang, Rodrigo Secolin, Clarissa Yasuda, Maxwell Kwok, Stefan Wolking, Felicitas Becker, Sarah Rau, Andreja Avbersek, Kristin Heggeli, Costin Leu, Chantal Depondt, Graeme J Sills, Anthony G Marson, Pauls Auce, Martin J Brodie, Ben Francis, Michael R Johnson, Bobby P C Koeleman, Pasquale Striano, Antonietta Coppola, Federico Zara, Wolfram S Kunz, Josemir W Sander, Holger Lerche, Karl Martin Klein, Sarah Weckhuysen, Martin Krenn, Lárus J Gudmundsson, Kári Stefánsson, Roland Krause, Neil Shear, Colin J D Ross, Norman Delanty, Munir Pirmohamed, Bruce C Carleton, Fernando Cendes, Iscia Lopes-Cendes, Wei-Ping Liao, Terence J O'Brien, Sanjay M Sisodiya, Stacey Cherny, Patrick Kwan, Larry Baum, Gianpiero L Cavalleri
OBJECTIVE: To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. METHODS: We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed...
December 29, 2017: Neurology
https://www.readbyqxmd.com/read/29286579/systematic-review-of-pharmacogenomics-and-adverse-drug-reactions-in-paediatric-oncology-patients
#13
REVIEW
Rachel Conyers, Subalatha Devaraja, David Elliott
Many paediatric patients with cancer experience significant chemotherapy side effects. Predisposition to drug reactions is governed by single nucleotide polymorphisms (SNPs). We performed a systematic review of the literature from 2006 through 2016. Outcomes of interest included patient characteristics, cancer type drug of interest, genes investigated, toxicity identified and genetic polymorphisms implicated. The primary toxicities studied were neurotoxicity cardiotoxicity, osteonecrosis, and thromboembolism and hypersensitivity reactions...
December 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29283396/pharmacogenomics-of-cyp2c9-functional-and-clinical-considerations
#14
REVIEW
Ann K Daly, Allan E Rettie, Douglas M Fowler, John O Miners
CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions...
December 28, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29283070/pharmacogenomics-of-methotrexate-current-status-and-future-outlook
#15
Mengda Cao, Miao Guo, De-Qin Wu, Ling Meng
BACKGROUND: Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a more efficient, compatible and cost-effective treatment of patients. OBJECTIVE: Present article aims to review genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcome, and try to point out future development directions of individualized MTX therapy...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29283068/influence-of-genetic-polymorphisms-on-mycophenolic-acid-pharmacokinetics-and-patient-outcomes-in-renal-transplantation
#16
Miao Guo, Zi-Jie Wang, Hai-Wei Yang, Ling Meng, Ruo-Yun Tan, Min Gu, Ji-Fu Wei
Mycophenolic acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA, involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and others...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29280137/multi-site-investigation-of-strategies-for-the-implementation-of-cyp2c19-genotype-guided-antiplatelet-therapy
#17
Philip E Empey, James M Stevenson, Sony Tuteja, Kristin W Weitzel, Dominick J Angiolillo, Amber L Beitelshees, James C Coons, Julio D Duarte, Francesco Franchi, Linda J B Jeng, Julie A Johnson, Rolf P Kreutz, Nita A Limdi, Kristin A Maloney, Aniwaa Owusu Obeng, Josh F Peterson, Natasha Petry, Victoria M Pratt, Fabiana Rollini, Stuart A Scott, Todd C Skaar, Mark R Vesely, George A Stouffer, Russell A Wilke, Larisa H Cavallari, Craig R Lee
CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program...
December 26, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29280110/-update-of-the-rome-iiii-criteria-for-functional-constipation
#18
Ting Yu, Liuqin Jiang, Lin Lin
The Rome IIII( criteria were released in May 2016. Based on the development of brain-intestinal axis theory, intestinal microecology, pharmacogenomics and social psychology, the Rome IIII( criteria revise the definition, diagnostic criteria, clinical evaluation process, and treatments of functional constipation (FC). The revisions are as follows: (1) Definition: FC and constipation-predominant irritable bowel syndrome are considered to be on a continuum rather than as independent entities. (2) Diagnostic criteria: the Bristol stool scale type 1, type 2 and spontaneous bowel movements are added in the diagnostic criteria, respectively, refining the criteria for stool consistency and frequency...
December 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/29261225/in-vitro-validation-of-mirna-mediated-gene-expression-linked-to-drug-metabolism
#19
Botros B Shenoda, Sujay Ramanathan, Seena K Ajit
Pharmacogenomic approaches used to investigate how genes affect drug responses are critical for designing personalized therapies aimed at maximizing efficacy and minimizing adverse effects. Drug efficacy is often dependent on the sequence and expression levels of drug target genes or those involved in the metabolism and transport of the therapeutic agent. Expression of these genes, in turn, is negatively regulated by small noncoding miRNAs. The levels of miRNAs in bodily fluids have been studied extensively as potential diagnostic and prognostic biomarkers...
December 20, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/29249361/pharmacogenomics-of-gpcr-drug-targets
#20
Alexander S Hauser, Sreenivas Chavali, Ikuo Masuho, Leonie J Jahn, Kirill A Martemyanov, David E Gloriam, M Madan Babu
Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug- and effector-binding sites in the human population...
December 8, 2017: Cell
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