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

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 t... Mehr ...

Verfasser: Kelly E. Caudle
Katrin Sangkuhl
Michelle Whirl‐Carrillo
Jesse J. Swen
Cyrine E. Haidar
Teri E. Klein
Roseann S. Gammal
Mary V. Relling
Stuart A. Scott
Daniel L. Hertz
Henk‐Jan Guchelaar
Andrea Gaedigk
Dokumenttyp: Artikel
Erscheinungsdatum: 2020
Reihe/Periodikum: Clinical and Translational Science, Vol 13, Iss 1, Pp 116-124 (2020)
Verlag/Hrsg.: Wiley
Schlagwörter: Therapeutics. Pharmacology / RM1-950 / Public aspects of medicine / RA1-1270
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27021748
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://doi.org/10.1111/cts.12692

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.