Identification of the primary gene defect at the cytochrome P450 CYP2D locus

Alan C. Gough, John S. Miles, Nigel K. Spurr, Julie E. Moss, Andrea Gaedigk, Michel Eichelbaum, C. Roland Wolf

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    Abstract

    THE mammalian cytochrome P450-dependent monooxygenase system is involved in the metabolism of drugs and chemical carcinogens1-5. The role of these enzymes in toxicological response is exemplified by an autosomal recessive polymorphism at the cytochrome P450 CYP2D6 debrisoquine hydroxylase locus which results in the severely compromised metabolism of at least 25 drugs, and which in some cases can lead to life-threatening side-effects3,6-12. In addition, this polymorphism, which affects 8-10% of the caucasian population, has been associated with altered susceptibility to lung and bladder cancer13-16. Here we report the identification of the primary mutation responsible for this metabolic defect and the development of a simple DNA-based genetic assay to allow both the identification of most individuals at risk of drug side-effects and clarification of the conflicting reports on the association of this polymorphism with cancer susceptibility13-18.

    Original languageEnglish
    Pages (from-to)773-776
    Number of pages4
    JournalNature
    Volume347
    Issue number6295
    DOIs
    Publication statusPublished - 25 Oct 1990

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    Gough, A. C., Miles, J. S., Spurr, N. K., Moss, J. E., Gaedigk, A., Eichelbaum, M., & Wolf, C. R. (1990). Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Nature, 347(6295), 773-776. https://doi.org/10.1038/347773a0