Methodology for clinical genotyping of CYP2D6 and CYP2C19
Abstract 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 methodolo...
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Nature Publishing Group
2021
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oai:doaj.org-article:16d854a36fa943aab4f32e69d4f3a3962021-11-28T12:09:31ZMethodology for clinical genotyping of CYP2D6 and CYP2C1910.1038/s41398-021-01717-92158-3188https://doaj.org/article/16d854a36fa943aab4f32e69d4f3a3962021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01717-9https://doaj.org/toc/2158-3188Abstract 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.Beatriz Carvalho HenriquesAvery BuchnerXiuying HuYabing WangVasyl YavorskyyKeanna WallaceRachael DongKristina MartensMichael S. CarrBahareh Behroozi AslJoshua HagueSudhakar SivapalanWolfgang MaierMojca Z. DernovsekNeven HenigsbergJoanna HauserDaniel SoueryAnnamaria CattaneoOle MorsMarcella RietschelGerald PfefferStacey HumeKatherine J. AitchisonNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-9 (2021) |
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| collection |
DOAJ |
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Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
| spellingShingle |
Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Beatriz Carvalho Henriques Avery Buchner Xiuying Hu Yabing Wang Vasyl Yavorskyy Keanna Wallace Rachael Dong Kristina Martens Michael S. Carr Bahareh Behroozi Asl Joshua Hague Sudhakar Sivapalan Wolfgang Maier Mojca Z. Dernovsek Neven Henigsberg Joanna Hauser Daniel Souery Annamaria Cattaneo Ole Mors Marcella Rietschel Gerald Pfeffer Stacey Hume Katherine J. Aitchison Methodology for clinical genotyping of CYP2D6 and CYP2C19 |
| description |
Abstract 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. |
| format |
article |
| author |
Beatriz Carvalho Henriques Avery Buchner Xiuying Hu Yabing Wang Vasyl Yavorskyy Keanna Wallace Rachael Dong Kristina Martens Michael S. Carr Bahareh Behroozi Asl Joshua Hague Sudhakar Sivapalan Wolfgang Maier Mojca Z. Dernovsek Neven Henigsberg Joanna Hauser Daniel Souery Annamaria Cattaneo Ole Mors Marcella Rietschel Gerald Pfeffer Stacey Hume Katherine J. Aitchison |
| author_facet |
Beatriz Carvalho Henriques Avery Buchner Xiuying Hu Yabing Wang Vasyl Yavorskyy Keanna Wallace Rachael Dong Kristina Martens Michael S. Carr Bahareh Behroozi Asl Joshua Hague Sudhakar Sivapalan Wolfgang Maier Mojca Z. Dernovsek Neven Henigsberg Joanna Hauser Daniel Souery Annamaria Cattaneo Ole Mors Marcella Rietschel Gerald Pfeffer Stacey Hume Katherine J. Aitchison |
| author_sort |
Beatriz Carvalho Henriques |
| title |
Methodology for clinical genotyping of CYP2D6 and CYP2C19 |
| title_short |
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_sort |
methodology for clinical genotyping of cyp2d6 and cyp2c19 |
| publisher |
Nature Publishing Group |
| publishDate |
2021 |
| url |
https://doaj.org/article/16d854a36fa943aab4f32e69d4f3a396 |
| work_keys_str_mv |
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| _version_ |
1718408123619737600 |