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Methodology for clinical genotyping of CYP2D6 and CYP2C19

Many antidepressants, atomoxetine, and several antipsychotics are metabolized by the cytochrome P450 enzymes CYP2D6 and CYP2C19, and guidelines for prescribers based on genetic variants exist. Although some laboratories offer such testing, there is no consensus regarding validated methodology for cl...

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Autores principales: Carvalho Henriques, Beatriz, Buchner, Avery, Hu, Xiuying, Wang, Yabing, Yavorskyy, Vasyl, Wallace, Keanna, Dong, Rachael, Martens, Kristina, Carr, Michael S., Behroozi Asl, Bahareh, Hague, Joshua, Sivapalan, Sudhakar, Maier, Wolfgang, Dernovsek, Mojca Z., Henigsberg, Neven, Hauser, Joanna, Souery, Daniel, Cattaneo, Annamaria, Mors, Ole, Rietschel, Marcella, Pfeffer, Gerald, Hume, Stacey, Aitchison, Katherine J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608805/
https://www.ncbi.nlm.nih.gov/pubmed/34811360
http://dx.doi.org/10.1038/s41398-021-01717-9
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author Carvalho Henriques, Beatriz
Buchner, Avery
Hu, Xiuying
Wang, Yabing
Yavorskyy, Vasyl
Wallace, Keanna
Dong, Rachael
Martens, Kristina
Carr, Michael S.
Behroozi Asl, Bahareh
Hague, Joshua
Sivapalan, Sudhakar
Maier, Wolfgang
Dernovsek, Mojca Z.
Henigsberg, Neven
Hauser, Joanna
Souery, Daniel
Cattaneo, Annamaria
Mors, Ole
Rietschel, Marcella
Pfeffer, Gerald
Hume, Stacey
Aitchison, Katherine J.
author_facet Carvalho Henriques, Beatriz
Buchner, Avery
Hu, Xiuying
Wang, Yabing
Yavorskyy, Vasyl
Wallace, Keanna
Dong, Rachael
Martens, Kristina
Carr, Michael S.
Behroozi Asl, Bahareh
Hague, Joshua
Sivapalan, Sudhakar
Maier, Wolfgang
Dernovsek, Mojca Z.
Henigsberg, Neven
Hauser, Joanna
Souery, Daniel
Cattaneo, Annamaria
Mors, Ole
Rietschel, Marcella
Pfeffer, Gerald
Hume, Stacey
Aitchison, Katherine J.
author_sort Carvalho Henriques, Beatriz
collection PubMed
description Many antidepressants, atomoxetine, and several antipsychotics are metabolized by the cytochrome P450 enzymes CYP2D6 and CYP2C19, and guidelines for prescribers based on genetic variants exist. Although some laboratories offer such testing, there is no consensus regarding validated methodology for clinical genotyping of CYP2D6 and CYP2C19. The aim of this paper was to cross-validate multiple technologies for genotyping CYP2D6 and CYP2C19 against each other, and to contribute to feasibility for clinical implementation by providing an enhanced range of assay options, customizable automated translation of data into haplotypes, and a workflow algorithm. AmpliChip CYP450 and some TaqMan single nucleotide variant (SNV) and copy number variant (CNV) data in the Genome-based therapeutic drugs for depression (GENDEP) study were used to select 95 samples (out of 853) to represent as broad a range of CYP2D6 and CYP2C19 genotypes as possible. These 95 included a larger range of CYP2D6 hybrid configurations than have previously been reported using inter-technology data. Genotyping techniques employed were: further TaqMan CNV and SNV assays, xTAGv3 Luminex CYP2D6 and CYP2C19, PharmacoScan, the Ion AmpliSeq Pharmacogenomics Panel, and, for samples with CYP2D6 hybrid configurations, long-range polymerase chain reactions (L-PCRs) with Sanger sequencing and Luminex. Agena MassARRAY was also used for CYP2C19. This study has led to the development of a broader range of TaqMan SNV assays, haplotype phasing methodology with TaqMan adaptable for other technologies, a multiplex genotyping method for efficient identification of some hybrid haplotypes, a customizable automated translation of SNV and CNV data into haplotypes, and a clinical workflow algorithm.
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spelling pubmed-86088052021-12-03 Methodology for clinical genotyping of CYP2D6 and CYP2C19 Carvalho Henriques, Beatriz Buchner, Avery Hu, Xiuying Wang, Yabing Yavorskyy, Vasyl Wallace, Keanna Dong, Rachael Martens, Kristina Carr, Michael S. Behroozi Asl, Bahareh Hague, Joshua Sivapalan, Sudhakar Maier, Wolfgang Dernovsek, Mojca Z. Henigsberg, Neven Hauser, Joanna Souery, Daniel Cattaneo, Annamaria Mors, Ole Rietschel, Marcella Pfeffer, Gerald Hume, Stacey Aitchison, Katherine J. Transl Psychiatry Article Many antidepressants, atomoxetine, and several antipsychotics are metabolized by the cytochrome P450 enzymes CYP2D6 and CYP2C19, and guidelines for prescribers based on genetic variants exist. Although some laboratories offer such testing, there is no consensus regarding validated methodology for clinical genotyping of CYP2D6 and CYP2C19. The aim of this paper was to cross-validate multiple technologies for genotyping CYP2D6 and CYP2C19 against each other, and to contribute to feasibility for clinical implementation by providing an enhanced range of assay options, customizable automated translation of data into haplotypes, and a workflow algorithm. AmpliChip CYP450 and some TaqMan single nucleotide variant (SNV) and copy number variant (CNV) data in the Genome-based therapeutic drugs for depression (GENDEP) study were used to select 95 samples (out of 853) to represent as broad a range of CYP2D6 and CYP2C19 genotypes as possible. These 95 included a larger range of CYP2D6 hybrid configurations than have previously been reported using inter-technology data. Genotyping techniques employed were: further TaqMan CNV and SNV assays, xTAGv3 Luminex CYP2D6 and CYP2C19, PharmacoScan, the Ion AmpliSeq Pharmacogenomics Panel, and, for samples with CYP2D6 hybrid configurations, long-range polymerase chain reactions (L-PCRs) with Sanger sequencing and Luminex. Agena MassARRAY was also used for CYP2C19. This study has led to the development of a broader range of TaqMan SNV assays, haplotype phasing methodology with TaqMan adaptable for other technologies, a multiplex genotyping method for efficient identification of some hybrid haplotypes, a customizable automated translation of SNV and CNV data into haplotypes, and a clinical workflow algorithm. Nature Publishing Group UK 2021-11-22 /pmc/articles/PMC8608805/ /pubmed/34811360 http://dx.doi.org/10.1038/s41398-021-01717-9 Text en © The Author(s) 2021, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Carvalho Henriques, Beatriz
Buchner, Avery
Hu, Xiuying
Wang, Yabing
Yavorskyy, Vasyl
Wallace, Keanna
Dong, Rachael
Martens, Kristina
Carr, Michael S.
Behroozi Asl, Bahareh
Hague, Joshua
Sivapalan, Sudhakar
Maier, Wolfgang
Dernovsek, Mojca Z.
Henigsberg, Neven
Hauser, Joanna
Souery, Daniel
Cattaneo, Annamaria
Mors, Ole
Rietschel, Marcella
Pfeffer, Gerald
Hume, Stacey
Aitchison, Katherine J.
Methodology for clinical genotyping of CYP2D6 and CYP2C19
title Methodology for clinical genotyping of CYP2D6 and CYP2C19
title_full Methodology for clinical genotyping of CYP2D6 and CYP2C19
title_fullStr Methodology for clinical genotyping of CYP2D6 and CYP2C19
title_full_unstemmed Methodology for clinical genotyping of CYP2D6 and CYP2C19
title_short Methodology for clinical genotyping of CYP2D6 and CYP2C19
title_sort methodology for clinical genotyping of cyp2d6 and cyp2c19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608805/
https://www.ncbi.nlm.nih.gov/pubmed/34811360
http://dx.doi.org/10.1038/s41398-021-01717-9
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