The Evaluation of <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> 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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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/5/661 |
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| author | Arianna Giorgetti Sara Amurri Giulia Fazio Carla Bini Laura Anniballi Filippo Pirani Guido Pelletti Susi Pelotti |
| author_facet | Arianna Giorgetti Sara Amurri Giulia Fazio Carla Bini Laura Anniballi Filippo Pirani Guido Pelletti Susi Pelotti |
| author_sort | Arianna Giorgetti |
| collection | DOAJ |
| 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 <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> 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 <i>CYP2D6, CYP2C9</i>, and <i>CYP2C19</i> 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. |
| first_indexed | 2024-03-11T03:30:21Z |
| format | Article |
| id | doaj.art-6ae2ac770cb94708ba7339cc8b00d15d |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T03:30:21Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-6ae2ac770cb94708ba7339cc8b00d15d2023-11-18T02:26:05ZengMDPI AGMetabolites2218-19892023-05-0113566110.3390/metabo13050661The Evaluation of <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> Phenoconversion in Post-Mortem Casework: The Challenge of Forensic ToxicogeneticsArianna Giorgetti0Sara Amurri1Giulia Fazio2Carla Bini3Laura Anniballi4Filippo Pirani5Guido Pelletti6Susi Pelotti7Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, ItalyUnit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, ItalyIn 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 <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> 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 <i>CYP2D6, CYP2C9</i>, and <i>CYP2C19</i> 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.https://www.mdpi.com/2218-1989/13/5/661drug metabolismdrug–gene interactioncytochrome P450 genesgenotypephenotypephenoconversion |
| spellingShingle | Arianna Giorgetti Sara Amurri Giulia Fazio Carla Bini Laura Anniballi Filippo Pirani Guido Pelletti Susi Pelotti The Evaluation of <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics Metabolites drug metabolism drug–gene interaction cytochrome P450 genes genotype phenotype phenoconversion |
| title | The Evaluation of <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics |
| title_full | The Evaluation of <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics |
| title_fullStr | The Evaluation of <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics |
| title_full_unstemmed | The Evaluation of <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics |
| title_short | The Evaluation of <i>CYP2D6, CYP2C9, CYP2C19</i>, and <i>CYP2B6</i> Phenoconversion in Post-Mortem Casework: The Challenge of Forensic Toxicogenetics |
| title_sort | evaluation of i cyp2d6 cyp2c9 cyp2c19 i and i cyp2b6 i phenoconversion in post mortem casework the challenge of forensic toxicogenetics |
| topic | drug metabolism drug–gene interaction cytochrome P450 genes genotype phenotype phenoconversion |
| url | https://www.mdpi.com/2218-1989/13/5/661 |
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