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 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.