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...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2020-01-01
|
Series: | Clinical and Translational Science |
Online Access: | https://doi.org/10.1111/cts.12692 |
id |
doaj-eaaeaa1c4346425da8183e2137c63c57 |
---|---|
record_format |
Article |
spelling |
doaj-eaaeaa1c4346425da8183e2137c63c572020-11-25T02:19:08ZengWileyClinical and Translational Science1752-80541752-80622020-01-0113111612410.1111/cts.12692Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working GroupKelly E. Caudle0Katrin Sangkuhl1Michelle Whirl‐Carrillo2Jesse J. Swen3Cyrine E. Haidar4Teri E. Klein5Roseann S. Gammal6Mary V. Relling7Stuart A. Scott8Daniel L. Hertz9Henk‐Jan Guchelaar10Andrea Gaedigk11Department of Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USADepartment of Biomedical Data Science Stanford University Stanford California USADepartment of Biomedical Data Science Stanford University Stanford California USADepartment of Clinical Pharmacy & Toxicology Leiden University Medical Center Leiden The NetherlandsDepartment of Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USADepartment of Biomedical Data Science Stanford University Stanford California USADepartment of Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USADepartment of Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis Tennessee USADepartment of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York New York USADepartment of Clinical Pharmacy University of Michigan College of Pharmacy Ann Arbor Michigan USADepartment of Clinical Pharmacy & Toxicology Leiden University Medical Center Leiden The NetherlandsDivision of Clinical Pharmacology, Toxicology, & Therapeutic Innovation Children's Mercy Kansas City Kansas City Missouri USATranslating 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.https://doi.org/10.1111/cts.12692 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group Clinical and Translational Science |
author_facet |
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 |
author_sort |
Kelly E. Caudle |
title |
Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group |
title_short |
Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group |
title_full |
Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group |
title_fullStr |
Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group |
title_full_unstemmed |
Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group |
title_sort |
standardizing cyp2d6 genotype to phenotype translation: consensus recommendations from the clinical pharmacogenetics implementation consortium and dutch pharmacogenetics working group |
publisher |
Wiley |
series |
Clinical and Translational Science |
issn |
1752-8054 1752-8062 |
publishDate |
2020-01-01 |
description |
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. |
url |
https://doi.org/10.1111/cts.12692 |
work_keys_str_mv |
AT kellyecaudle standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT katrinsangkuhl standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT michellewhirlcarrillo standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT jessejswen standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT cyrineehaidar standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT terieklein standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT roseannsgammal standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT maryvrelling standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT stuartascott standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT daniellhertz standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT henkjanguchelaar standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup AT andreagaedigk standardizingcyp2d6genotypetophenotypetranslationconsensusrecommendationsfromtheclinicalpharmacogeneticsimplementationconsortiumanddutchpharmacogeneticsworkinggroup |
_version_ |
1724878287574925312 |