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

Nature volume 347, pages 773–776 (1990)Cite this article

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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Author information

Author notes

  1. John S. Miles

    Present address: Department of Biochemistry, University of Glasgow, Glasgow, G12 8QQ, UK

  2. C. Roland Wolf: To whom correspondence should be addressed

Authors and Affiliations

  1. Imperial Cancer Research Fund, Human Genetic Resources, Clare Hall Laboratories, South Mimms, Potters Bar, EN6 3LD, UK

    Alan C. Gough & Nigel K. Spurr

  2. Imperial Cancer Research Fund, Molecular Pharmacology Group, University Department of Biochemistry, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK

    John S. Miles, Julie E. Moss & C. Roland Wolf

  3. Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, AuerbaChStraSSe 112, D-7000, Stuttgart, 50, Germany

    Andrea Gaedigk & Michel Eichelbaum

Authors
  1. Alan C. Gough
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  2. John S. Miles
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  3. Nigel K. Spurr
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  4. Julie E. Moss
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  5. Andrea Gaedigk
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  6. Michel Eichelbaum
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  7. C. Roland Wolf
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Gough, A., Miles, J., Spurr, N. et al. Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Nature 347, 773–776 (1990). https://doi.org/10.1038/347773a0

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