Fatal intoxication cases: cytochrome P450 2D6 and 2C19 genotype distributions
2004 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, Vol. 60, no 8, 547-552 p.Article in journal (Refereed) Published
OBJECTIVE: Many commonly used pharmaceuticals, such as antidepressants and neuroleptics as well as some illegal drugs, are metabolised by the cytochrome P450 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.
Place, publisher, year, edition, pages
2004. Vol. 60, no 8, 547-552 p.
CYP2D6, CYP2C19, Post-mortem
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-17933DOI: 10.1007/s00228-004-0800-xPubMedID: 15349706OAI: oai:DiVA.org:liu-17933DiVA: diva2:213007