"It's the genes, stupid". Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism

Life Sci. 1995;56(26):2285-98. doi: 10.1016/0024-3205(95)00223-s.


In this review we highlight the information available on the genetic polymorphism of cytochrome P4502D6 expression in man. An absent function of this enzyme is observed in 7-10 percent of the Caucasian population which are referred to as Poor metabolizers as opposed to the remainder of the population (Extensive Metabolizers). More than 30 widely used drugs have been identified as substrates for CYP2D6. Disposition and action of these compounds depend on the individual phenotype. Both the molecular bases of the variable enzyme activity and the consequences for drug therapy are outlined. While mutations on the DNA level have been investigated in great detail larger scale clinical trials are lacking and information on therapeutic consequences of CYP2D6 mediated polymorphic drug oxidation is restricted to case reports. Besides these implications for drug metabolism several lines of evidence indicate that CYP2D6 could be involved in biotransformation of endogenous compounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Oxidation-Reduction
  • Pharmaceutical Preparations / metabolism
  • Polymorphism, Genetic*


  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2D6