Cytochrome P450 CYP2D6

    Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

    49 Citations (Scopus)

    Abstract

    Altered expression of CYP2D6 (debrisoquine hydroxylase), resulting from genetic polymorphism at the CYP2D6 gene locus, is responsible for pronounced interindividual variation in the metabolism of many clinically important drugs. Although CYP2D6 substrates are structurally diverse, most are small molecules that interact with the protein via an electrostatic interaction between a basic nitrogen which is common to the majority of CYP2D6 substrates and an aspartic acid residue in the active site of the protein. As CYP2D6 substrates have a wide range of pharmacological functions, any variation in CYP2D6 expression can have profound clinical consequences. CYP2D6 activity can be determined both by phenotyping methods with a variety of probe drugs and by genotyping methods where PCR-based techniques are used to investigate the inheritance of individual CYP2D6 alleles. Allele frequencies have been shown to vary widely between populations of different racial origin. For example, the PM genotype is particularly rare in Orientals. The inheritance of certain CYP2D6 allelic variants has been associated with altered susceptibility to Parkinson's disease and several types of cancer.
    Original languageEnglish
    Title of host publicationMetabolic Polymorphisms and Susceptibility to Cancer
    PublisherInternational Agency for Research on Cancer
    Pages209-29
    Number of pages21
    Volume148
    ISBN (Print)978-92-832-2148-7
    Publication statusPublished - 1999

    Publication series

    NameIARC Scientific Publications
    PublisherIARC
    ISSN (Print)0300-5038

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    Cite this

    Wolf, C. R., & Smith, G. (1999). Cytochrome P450 CYP2D6. In Metabolic Polymorphisms and Susceptibility to Cancer (Vol. 148, pp. 209-29). (IARC Scientific Publications). International Agency for Research on Cancer . http://publications.iarc.fr/Book-And-Report-Series/Iarc-Scientific-Publications/Metabolic-Polymorphisms-And-Susceptibility-To-Cancer-1999