Toxicogenetics--cytochrome P450 microarray analysis in forensic cases focusing on morphine/codeine and diazepam
H Andresen1, C Augustin, T Streichert
1Institute of Legal Medicine, Forensic Toxicology, University Medical Center Hamburg-Eppendorf, Butenfeld 34, 22529, Hamburg, Germany. h.andresen@uke.uni-hamburg.de
International Journal of Legal Medicine
|August 18, 2012
Summary
Genetic polymorphisms in cytochrome P450 (CYP) enzymes can alter drug metabolism. This pilot study found toxicogenetics moderately relevant in forensic cases, with genetic testing occasionally providing crucial insights into drug metabolism discrepancies.
Area of Science:
- Forensic Toxicology
- Pharmacogenetics
- Clinical Chemistry
Background:
- Genetic variations in cytochrome P450 (CYP) enzymes influence drug metabolism.
- Genotype-based dosing is crucial in pharmacotherapy.
- The utility of genetic testing in forensic investigations is under exploration.
Purpose of the Study:
- To evaluate the routine application of genetic polymorphism testing in forensic cases.
- To investigate if CYP2D6 and CYP2C19 genetic variations explain unusual drug metabolite ratios.
- To assess the impact of genetic factors versus drug-drug interactions in forensic casework.
Main Methods:
- Screening of routine forensic cases (2004-2008) for unusual parent compound to metabolite (P/M) ratios.
- Genotyping for CYP2D6 and CYP2C19 polymorphisms using Roche AmpliChip.
- Gas chromatography/mass spectrometry (GC/MS) for drug analysis when needed.
Main Results:
- Eleven samples showed conspicuous P/M ratios.
- Identified CYP2D6 poor metabolizers (PM) and intermediate metabolizers (IM).
- Identified CYP2C19 intermediate metabolizers (IM); only one case was clearly explained by genetic polymorphism, with drug-drug interactions being more frequent.
Conclusions:
- Toxicogenetics has moderate overall relevance in forensic toxicology.
- Intermediate metabolizer (IM) genotypes may be more significant than previously thought.
- Genetic testing can provide valuable insights in specific forensic cases.
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