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Pharmacogenomics review

Celia N Sanchez-Dominguez, Hugo L Gallardo-Blanco, Mauricio A Salinas-Santander, Rocio Ortiz-Lopez
Biotransformation is an enzyme-catalyzed process in which the body converts endogenous compounds, xenobiotics and toxic substances into harmless or easily excreted metabolites. The biotransformation reactions are classified as phase I and II reactions. Uridine 5'-diphospho (UDP)-glucuronosyltransferases (UGTs) are a superfamily of phase II enzymes which have roles in the conjugation of xenobiotics or endogenous compounds, including drugs and bilirubin, with glucuronic acid to make them easier to excrete. The method the human body uses to achieve glucuronidation may be affected by a large interindividual variation due to changes in the sequences of the genes encoding these enzymes...
July 2018: Experimental and Therapeutic Medicine
Michael T Eadon, Sri H Kanuri, Arlene B Chapman
Introduction: Increasing clinical evidence supports the implementation of genotyping for anti-hypertensive drug dosing and selection. Despite robust evidence gleaned from clinical trials, the translation of genotype guided therapy into clinical practice faces significant challenges. Challenges to implementation include the small effect size of individual variants and the polygenetic nature of antihypertensive drug response, a lack of expert consensus on dosing guidelines even without genetic information, and proper definition of major antihypertensive drug toxicities...
2018: Expert Review of Precision Medicine and Drug Development
Mou-Ze Liu, Hai-Yan He, Jian-Quan Luo, Fa-Zhong He, Zhang-Ren Chen, Yi-Ping Liu, Da-Xiong Xiang, Hong-Hao Zhou, Wei Zhang
Drug-induced diabetes is widely reported in clinical conditions, and it is becoming a global issue because of its potential to increase the risk of severe cardiovascular complications. However, which drug mechanisms exert their diabetogenic effects and why the effects present significant inter-individual differences remain largely unknown. Pharmacogenomics, which is the study of how genomic variation influences drug responses, provides an explanation for individual differences in drug-induced diabetes. We highlight that pharmacogenomics can be involved in regulating the expression of genes in signaling pathways related to the pharmacokinetics or pharmacodynamics of drugs or the pathogenesis of diabetes, contributing to the differences in drug-induced glucose impairment...
June 1, 2018: Archives of Pharmacal Research
Azzurra Orlandi, Maria Chiara Paolino, Pasquale Striano, Pasquale Parisi
Although novel antiepileptic drugs (AEDs) have been recently released, the issue of drug resistance in epileptic patients remains unsolved and largely unpredictable. Areas covered: We aim to assess the clinical impact of genetic variations that may influence the efficacy of medical treatment in epilepsy patients. Indeed, many genes, including genes encoding drug transporters (ABCB1), drug targets (SCN1A), drug-metabolizing enzymes (CYP2C9, CYP2C19), and human leucocyte antigen (HLA) proteins, may regulate the mechanisms of drug resistance in epilepsy...
May 2018: Expert Opinion on Drug Metabolism & Toxicology
Paul C D Bank, Jesse J Swen, Henk-Jan Guchelaar
Currently, germline pharmacogenomics (PGx) is successfully implemented within certain specialties in clinical care. With the integration of PGx in pharmacotherapy multiple stakeholders are involved, which are identified in this chapter. Clinically relevant pharmacogenes with their related PGx test are discussed, along with diagnostic test criteria to guide clinicians and policy makers in PGx test selection. The chapter further reviews the similarities and the differences between the guidelines of the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium which both support healthcare professionals in understanding PGx test results and help guiding pharmacotherapy by providing evidence-based dosing recommendations...
2018: Advances in Pharmacology
Guilherme Suarez-Kurtz, Esteban J Parra
Pharmacogenetics/pharmacogenomics (PGx) relies on human genetic diversity. In this review we initially examine the PGx implications of human demographic history and genetic diversity, and highlight results from recent studies on the worldwide distribution of common and rare variants in pharmacogenes. The abundance of rare variants implies that a substantial effort will be required to identify their putative functional effects and to develop reliable algorithms for PGx-guided prescription. Furthermore, variants in all pharmacogenes relevant to a drug treatment must be considered...
2018: Advances in Pharmacology
José A G Agúndez, Javier Gómez-Tabales, Francisco Ruano, Elena García-Martin
PURPOSE OF REVIEW: The aim of the present review is to discuss recent advances supporting a role of paracetamol metabolism in hypersensitivity reactions to this drug. RECENT FINDINGS: Recent developments in the identification of novel paracetamol metabolites, as well as in allele frequencies and functional effects of genetic variation leading to the bioavailablity of reactive paracetamol metabolites, have led to the identification of potential pharmacogenomic and metabolomic targets in studies seeking mechanisms involved in hypersensitivity reactions caused by this drug...
May 22, 2018: Current Opinion in Allergy and Clinical Immunology
Shani Stern, Sara Linker, Krishna C Vadodaria, Maria C Marchetto, Fred H Gage
Personalized medicine has become increasingly relevant to many medical fields, promising more efficient drug therapies and earlier intervention. The development of personalized medicine is coupled with the identification of biomarkers and classification algorithms that help predict the responses of different patients to different drugs. In the last 10 years, the Food and Drug Administration (FDA) has approved several genetically pre-screened drugs labelled as pharmacogenomics in the fields of oncology, pulmonary medicine, gastroenterology, haematology, neurology, rheumatology and even psychiatry...
May 2018: Open Biology
Robert D Beckett, David F Kisor, Thomas Smith, Brooke Vonada
AIM: To systematically assess methodological quality of pharmacogenomics clinical practice guidelines. METHODS: Guidelines published through 2017 were reviewed by at least three independent reviewers using the AGREE II instrument, which consists of 23 items grouped into 6 domains and 2 items representing an overall assessment. Items were assessed on a seven-point rating scale, and aggregate quality scores were calculated. RESULTS: 31 articles were included...
June 1, 2018: Pharmacogenomics
Claudia Pisanu, Urs Heilbronner, Alessio Squassina
Bipolar disorder (BD) is a common and disabling psychiatric condition with a severe socioeconomic impact. BD is treated with mood stabilizers, among which lithium represents the first-line treatment. Lithium alone or in combination is effective in 60% of chronically treated patients, but response remains heterogenous and a large number of patients require a change in therapy after several weeks or months. Many studies have so far tried to identify molecular and genetic markers that could help us to predict response to mood stabilizers or the risk for adverse drug reactions...
May 22, 2018: Molecular Diagnosis & Therapy
Christine Y Lu, Stephanie Loomer, Rachel Ceccarelli, Kathleen M Mazor, James Sabin, Ellen Wright Clayton, Geoffrey S Ginsburg, Ann Chen Wu
Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 private payers for 23 biomarkers (e.g., HER2 and EGFR ) and multi-gene tests. We extracted policy coverage and criteria, prior authorization requirements, and an evidence basis for coverage. We reviewed professional society guidelines and their recommendations for use of pharmacogenomic tests...
May 16, 2018: Journal of Personalized Medicine
Nina Pirih, Tanja Kunej
The volume of publications and the type of research approaches used in omics system sciences are vast and continue to expand rapidly. This increased complexity and heterogeneity of omics data are challenging data extraction, sensemaking, analyses, knowledge translation, and interpretation. An extended and dynamic taxonomy for the classification and summary of omics studies are essential. We present an updated taxonomy for classification of omics research studies based on four criteria: (1) type and number of genomic loci in a research study, (2) number of species and biological samples, (3) the type of omics technology (e...
May 2018: Omics: a Journal of Integrative Biology
Chuan Wu, Wei Li
Acute lymphoblastic leukaemia (ALL) is a prevalent form of pediatric cancer that accounts for 70-80% of all leukemias. Genome-based analysis, exome sequencing, transcriptomics and proteomics have provided insight into genetic classification of ALL and helped identify novel subtypes of the disease. B and T cell-based ALL are two well-characterized genomic subtypes, significantly marked by bone marrow disorders, along with mutations in trisomy 21 and T53. The other ALLs include Early T-cell precursor ALL, Philadelphia chromosome-like ALL, Down syndrome-associated ALL and Relapsed ALL...
June 2018: Critical Reviews in Oncology/hematology
Lucila Ohno-Machado, Jihoon Kim, Rodney A Gabriel, Grace M Kuo, Michael A Hogarth
Several reviews and case reports have described how information derived from the analysis of genomes are currently included in electronic health records (EHRs) for the purposes of supporting clinical decisions. Since the introduction of this new type of information in EHRs is relatively new (for instance, the widespread adoption of EHRs in the United States is just about a decade old), it is not surprising that a myriad of approaches has been attempted, with various degrees of success. EHR systems undergo much customization to fit the needs of health systems; these approaches have been varied and not always generalizable...
May 1, 2018: Human Molecular Genetics
Vivian Y Chang, Jessica J Wang
PURPOSE OF REVIEW: The goal of this review is to summarize current understanding of pharmacogenetics and pharmacogenomics in chemotherapy-induced cardiotoxicity. RECENT FINDINGS: Most of the studies rely on in vitro cytotoxic assays. There have been several smaller scale candidate gene approaches and a handful of genome-wide studies linking genetic variation to susceptibility to chemotherapy-induced cardiotoxicity. Currently, pharmacogenomic testing of all childhood cancer patients with an indication for doxorubicin or daunorubicin therapy for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 variants is recommended...
April 30, 2018: Current Oncology Reports
Michael Camilleri
The objectives are to review the role of pharmacogenomics in drug metabolism of medications typically used in patients with irritable bowel syndrome (IBS) focusing predominantly on cytochrome P450 metabolism. Other aims are to provide examples of genetic variation of receptors or intermediary pathways that are targets for IBS drugs and to critically appraise the situations where precision medicine is impacting health in IBS. Pharmacogenomics impacts both pharmacokinetics and pharmacodynamics. Although large clinical trials have not incorporated testing for genetic variations that could impact the efficacy of medications in IBS, there are therapeutic advantages to inclusion of pharmacogenomics testing for individual patients, as has been demonstrated particularly in the treatment with central neuromodulators in psychiatry practice...
April 27, 2018: Clinical Gastroenterology and Hepatology
Li Hao, Shi Fang-Hong, Huang Shi-Ying, Zhang Shun-Guo, Chen Min-Ling
Natalizumab (Tysabri®, Biogen-Idec Inc., NAT), a humanized anti-α4 integrin monoclonal antibody, binds in both α4β1 (Very Late Antigen 4, VLA-4) and α4β7 (lymphocytes Peyer's patch adhesion molecule 1, LPAM-1) integrins, is approved for the treatment of Multiple sclerosis (MS) and Crohn's disease (CD). NAT has been well tolerated in pivotal trials. Progressive multifocal leukoencephalopathy (PML) is an uncommon but serious complications resulting from NAT treatment. It is not confirmed that higher NAT concentration increases the risk of PML...
April 27, 2018: Current Drug Metabolism
Marwah Doestzada, Arnau Vich Vila, Alexandra Zhernakova, Debby P Y Koonen, Rinse K Weersma, Daan J Touw, Folkert Kuipers, Cisca Wijmenga, Jingyuan Fu
Inter-individual heterogeneity in drug response is a serious problem that affects the patient's wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recognized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition...
April 28, 2018: Protein & Cell
Letícia C Tavares, Leiliane R Marcatto, Paulo Cjl Santos
Warfarin pharmacogenomics has been an extensively studied field in the last decades as it is focused on personalized therapy to overcome the wide interpatient warfarin response variability and decrease the risk of side effects. In this expert review, besides briefly summarizing the current knowledge about warfarin pharmacogenetics, we also present an overview of recent studies that aimed to assess the efficacy, safety and economic issues related to genotype-based dosing algorithms used to guide warfarin therapy, including randomized and controlled clinical trials, meta-analyses and cost-effectiveness studies...
April 27, 2018: Pharmacogenomics
Dan M Roden, Sara L Van Driest, Quinn S Wells, Jonathan D Mosley, Joshua C Denny, Josh F Peterson
This review will provide an overview of the principles of pharmacogenomics from basic discovery to implementation, encompassing application of tools of contemporary genome science to the field (including areas of apparent divergence from disease-based genomics), a summary of lessons learned from the extensively studied drugs clopidogrel and warfarin, the current status of implementing pharmacogenetic testing in practice, the role of genomics and related tools in the drug development process, and a summary of future opportunities and challenges...
April 27, 2018: Circulation Research
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