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The Evaluation of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics

In toxicogenetics, an integrative approach including the prediction of phenotype based on post-mortem genotyping of drug-metabolising enzymes might help explain the cause of death (CoD) and manner of death (MoD). The use of concomitant drugs, however, might lead to phenoconversion, a mismatch betwee...

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Autores principales: Giorgetti, Arianna, Amurri, Sara, Fazio, Giulia, Bini, Carla, Anniballi, Laura, Pirani, Filippo, Pelletti, Guido, Pelotti, Susi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221100/
https://www.ncbi.nlm.nih.gov/pubmed/37233702
http://dx.doi.org/10.3390/metabo13050661
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author Giorgetti, Arianna
Amurri, Sara
Fazio, Giulia
Bini, Carla
Anniballi, Laura
Pirani, Filippo
Pelletti, Guido
Pelotti, Susi
author_facet Giorgetti, Arianna
Amurri, Sara
Fazio, Giulia
Bini, Carla
Anniballi, Laura
Pirani, Filippo
Pelletti, Guido
Pelotti, Susi
author_sort Giorgetti, Arianna
collection PubMed
description In toxicogenetics, an integrative approach including the prediction of phenotype based on post-mortem genotyping of drug-metabolising enzymes might help explain the cause of death (CoD) and manner of death (MoD). The use of concomitant drugs, however, might lead to phenoconversion, a mismatch between the phenotype based on the genotype and the metabolic profile actually observed after phenoconversion. The aim of our study was to evaluate the phenoconversion of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 drug-metabolising enzymes in a series of autopsy cases tested positive for drugs that are substrates, inducers, or inhibitors of these enzymes. Our results showed a high rate of phenoconversion for all enzymes and a statistically significant higher frequency of poor and intermediate metabolisers for CYP2D6, CYP2C9, and CYP2C19 after phenoconversion. No association was found between phenotypes and CoD or MoD, suggesting that, although phenoconversion might be useful for a forensic toxicogenetics approach, more research is needed to overcome the challenges arising from the post-mortem setting.
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spelling pubmed-102211002023-05-28 The Evaluation of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics Giorgetti, Arianna Amurri, Sara Fazio, Giulia Bini, Carla Anniballi, Laura Pirani, Filippo Pelletti, Guido Pelotti, Susi Metabolites Article In toxicogenetics, an integrative approach including the prediction of phenotype based on post-mortem genotyping of drug-metabolising enzymes might help explain the cause of death (CoD) and manner of death (MoD). The use of concomitant drugs, however, might lead to phenoconversion, a mismatch between the phenotype based on the genotype and the metabolic profile actually observed after phenoconversion. The aim of our study was to evaluate the phenoconversion of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 drug-metabolising enzymes in a series of autopsy cases tested positive for drugs that are substrates, inducers, or inhibitors of these enzymes. Our results showed a high rate of phenoconversion for all enzymes and a statistically significant higher frequency of poor and intermediate metabolisers for CYP2D6, CYP2C9, and CYP2C19 after phenoconversion. No association was found between phenotypes and CoD or MoD, suggesting that, although phenoconversion might be useful for a forensic toxicogenetics approach, more research is needed to overcome the challenges arising from the post-mortem setting. MDPI 2023-05-16 /pmc/articles/PMC10221100/ /pubmed/37233702 http://dx.doi.org/10.3390/metabo13050661 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Giorgetti, Arianna
Amurri, Sara
Fazio, Giulia
Bini, Carla
Anniballi, Laura
Pirani, Filippo
Pelletti, Guido
Pelotti, Susi
The Evaluation of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics
title The Evaluation of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics
title_full The Evaluation of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics
title_fullStr The Evaluation of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics
title_full_unstemmed The Evaluation of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics
title_short The Evaluation of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics
title_sort evaluation of cyp2d6, cyp2c9, cyp2c19, and cyp2b6 phenoconversion in post-mortem casework: the challenge of forensic toxicogenetics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221100/
https://www.ncbi.nlm.nih.gov/pubmed/37233702
http://dx.doi.org/10.3390/metabo13050661
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