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Fatal intoxication cases: cytochrome P 450 2D6 and 2C19 genotype distributions

  • Pharmacogenetics
  • Published:
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Abstract

Objective

Many commonly used pharmaceuticals, such as antidepressants and neuroleptics as well as some illegal drugs, are metabolised by the cytochrome P 450 enzyme debrisoquine 4-hydroxylase (CYP2D6). Of Caucasians, 7–10% lack this enzyme, which can, upon administration of drugs in normal therapeutic doses, lead to adverse reactions and unexpected intoxication, leading in turn even to a fatal outcome in some cases.

Methods

Individuals (n=242) who had died due to intoxication by pharmaceuticals were genotyped for CYP2D6 and CYP2C19 and compared with a reference group of 281 blood donors. A single nucleotide polymorphism (SNP) method was used to identify five CYP2D6 alleles: *1 (wt), *2, *3, *4 and *6. The allele *5, a complete gene deletion, was identified by a multiplex amplification of long DNA fragments. Four CYP2C19 alleles *1 (wt), *2, *3 and *4 were also identified by SNP analysis.

Results

The prevalence of the CYP2D6 poor metaboliser (PM) genotypes in individuals with fatal intoxication was lower (4.7%) than expected from the frequencies of these genotypes in the blood donors (8.5%). A significantly lower frequency P<0.005 (0.03 with correction according to Bonferroni) was found for the CYP2D6*4 allele among the fatal intoxication cases. The CYP2C19 genotype analyses showed the same results for the fatal intoxication cases and for the blood donors.

Conclusions

The findings in this study confirm our earlier observations of a lower frequency of CYP2D6 PM genotypes in cases of fatal intoxication. To our knowledge, it has not been shown previously that intoxication victims might have a lower frequency of PMs than the general population.

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Acknowledgements

This work has been supported by grants from the National Board of Forensic Medicine (Rättsmedicinalverket), Sweden.

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Authors and Affiliations

  1. National Board of Forensic Medicine, Department of Forensic Genetics, , University Hospital, 581 85, Linköping, Sweden

    A. L. Zackrisson, A. B. Gladh & B. Lindblom

  2. National Board of Forensic Medicine, Department of Forensic Chemistry, University Hospital, 581 85, Linköping, Sweden

    P. Holmgren & J. Ahlner

Authors
  1. A. L. Zackrisson
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  2. P. Holmgren
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  3. A. B. Gladh
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  4. J. Ahlner
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  5. B. Lindblom
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Corresponding author

Correspondence to A. L. Zackrisson.

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Zackrisson, A.L., Holmgren, P., Gladh, A.B. et al. Fatal intoxication cases: cytochrome P 450 2D6 and 2C19 genotype distributions. Eur J Clin Pharmacol 60, 547–552 (2004). https://doi.org/10.1007/s00228-004-0800-x

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  • DOI: https://doi.org/10.1007/s00228-004-0800-x

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