Giorgetti Arianna, Amurri Sara, Fazio Giulia, Bini Carla, Anniballi Laura, Pirani Filippo, Pelletti Guido, Pelotti Susi
Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy.
Metabolites. 2023 May 16;13(5):661. doi: 10.3390/metabo13050661.
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 , and 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 , and 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.
在毒理遗传学中，一种综合方法，包括基于药物代谢酶的死后基因分型预测表型，可能有助于解释死亡原因（CoD）和死亡方式（MoD）。然而，同时使用药物可能会导致表型转换，即基于基因型的表型与表型转换后实际观察到的代谢谱之间不匹配。我们研究的目的是评估在一系列对这些酶的底物、诱导剂或抑制剂药物检测呈阳性的尸检病例中，、和药物代谢酶的表型转换情况。我们的结果显示，所有酶的表型转换率都很高，并且在表型转换后，、和代谢不良和中等代谢者的频率在统计学上显著更高。未发现表型与CoD或MoD之间存在关联，这表明，尽管表型转换可能有助于法医毒理遗传学方法，但仍需要更多研究来克服死后环境带来的挑战。
