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

    Research output: Contribution to journalArticle

    307 Citations (Scopus)

    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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    Cytochrome P-450 CYP2D6
    Cytochrome P-450 Enzyme System
    Mixed Function Oxygenases
    Drug-Related Side Effects and Adverse Reactions
    Pharmaceutical Preparations
    Toxicology
    Genes
    Urinary Bladder
    Lung
    Mutation
    DNA
    Enzymes
    Population
    Neoplasms

    Cite this

    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
    Gough, Alan C. ; Miles, John S. ; Spurr, Nigel K. ; Moss, Julie E. ; Gaedigk, Andrea ; Eichelbaum, Michel ; Wolf, C. Roland. / Identification of the primary gene defect at the cytochrome P450 CYP2D locus. In: Nature. 1990 ; Vol. 347, No. 6295. pp. 773-776.
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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.",
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    Gough, AC, Miles, JS, Spurr, NK, Moss, JE, Gaedigk, A, Eichelbaum, M & Wolf, CR 1990, 'Identification of the primary gene defect at the cytochrome P450 CYP2D locus', Nature, vol. 347, no. 6295, pp. 773-776. https://doi.org/10.1038/347773a0

    Identification of the primary gene defect at the cytochrome P450 CYP2D locus. / Gough, Alan C.; Miles, John S.; Spurr, Nigel K.; Moss, Julie E.; Gaedigk, Andrea; Eichelbaum, Michel; Wolf, C. Roland.

    In: Nature, Vol. 347, No. 6295, 25.10.1990, p. 773-776.

    Research output: Contribution to journalArticle

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    Gough AC, Miles JS, Spurr NK, Moss JE, Gaedigk A, Eichelbaum M et al. Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Nature. 1990 Oct 25;347(6295):773-776. https://doi.org/10.1038/347773a0