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      Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines

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          Abstract

          Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Réseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient’s genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename “extensive metabolizer (EM)” to “normal metabolizer (NM)”. It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders.

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          Most cited references63

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          Pharmacogenetics: from bench to byte--an update of guidelines.

          Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
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            Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.

            Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org).
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              A Genotype-Guided Strategy for Oral P2Y 12 Inhibitors in Primary PCI

              It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                25 January 2021
                2020
                : 11
                : 595219
                Affiliations
                [ 1 ]Division of Laboratories, Pharmacy, and Biomedical Genetics, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands
                [ 2 ]Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, Netherlands
                [ 3 ]Royal Dutch Pharmacists Association (KNMP), Hague, Netherlands
                Author notes
                *Correspondence: Vera H. M. Deneer, V.H.M.Deneer@ 123456umcutrecht.nl

                This article was submitted to Pharmacogenetics and Pharmacogenomics, a section of the journal Frontiers in Pharmacology

                Edited by: Henk-Jan Guchelaar, Leiden University Medical Center, Netherlands

                Reviewed by: Kelly Caudle, St. Jude Children's Research Hospital, United States

                Stuart Scott, Icahn School of Medicine at Mount Sinai, United States

                Article
                595219
                10.3389/fphar.2020.595219
                7868558
                33568995
                b0c237ac-c07f-4da7-a60e-9b4edacea192
                Copyright © 2021 Abdullah-Koolmees, van Keulen, Nijenhuis and Deneer.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 August 2020
                : 30 October 2020
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                pharmacogenetics,guidelines,pharmacogenomics,dpwg,cpic,cpnds,rnpgx,recommendations

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