Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group.

Autor: Caudle KE; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Sangkuhl K; Department of Biomedical Data Science, Stanford University, Stanford, California, USA., Whirl-Carrillo M; Department of Biomedical Data Science, Stanford University, Stanford, California, USA., Swen JJ; Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Haidar CE; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Klein TE; Department of Biomedical Data Science, Stanford University, Stanford, California, USA., Gammal RS; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.; Department of Pharmacy Practice, MCPHS University School of Pharmacy, Boston, Massachusetts, USA., Relling MV; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Scott SA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Sema4, a Mount Sinai venture, Stamford, Connecticut, USA., Hertz DL; Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA., Guchelaar HJ; Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Gaedigk A; Division of Clinical Pharmacology, Toxicology, & Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, Missouri, USA.; School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA.
Jazyk: angličtina
Zdroj: Clinical and translational science [Clin Transl Sci] 2020 Jan; Vol. 13 (1), pp. 116-124. Date of Electronic Publication: 2019 Oct 24.
DOI: 10.1111/cts.12692
Abstrakt: Translating CYP2D6 genotype to metabolizer phenotype is not standardized across clinical laboratories offering pharmacogenetic (PGx) testing and PGx clinical practice guidelines, such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). The genotype to phenotype translation discordance between laboratories and guidelines can cause discordant cytochrome P450 2D6 (CYP2D6) phenotype assignments and, thus lead to inconsistent therapeutic recommendations and confusion among patients and clinicians. A modified-Delphi method was used to obtain consensus for a uniform system for translating CYP2D6 genotype to phenotype among a panel of international CYP2D6 experts. Experts with diverse involvement in CYP2D6 interpretation (clinicians, researchers, genetic testing laboratorians, and PGx implementers; n = 37) participated in conference calls and surveys. After completion of 7 surveys, a consensus (> 70%) was reached with 82% of the CYP2D6 experts agreeing to the final CYP2D6 genotype to phenotype translation method. Broad adoption of the proposed CYP2D6 genotype to phenotype translation method by guideline developers, such as CPIC and DPWG, and clinical laboratories as well as researchers will result in more consistent interpretation of CYP2D6 genotype.
(© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje