Identification of the Primary Gene Defect at the Cytochrome P450 CYP2D Locus

Nature. 1990 Oct 25;347(6295):773-6. doi: 10.1038/347773a0.


The mammalian cytochrome P450-dependent monooxygenase system is involved in the metabolism of drugs and chemical carcinogens. 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-effects. In addition, this polymorphism, which affects 8-10% of the caucasian population, has been associated with altered susceptibility to lung and bladder cancer. 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 susceptibility.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 Enzyme System / genetics*
  • Deoxyribonucleases, Type II Site-Specific
  • Humans
  • Lung Neoplasms / genetics
  • Mixed Function Oxygenases / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Urinary Bladder Neoplasms / genetics


  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2D6
  • endodeoxyribonuclease XBAI
  • Deoxyribonucleases, Type II Site-Specific

Associated data

  • GENBANK/X16865
  • GENBANK/X16866
  • GENBANK/X16867