Cytochrome P450 CYP2D6

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

    48 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
    Pages209-29
    Number of pages21
    Volume148
    Publication statusPublished - 1999

    Publication series

    NameIARC Scientific Publications
    PublisherIARC
    ISSN (Print)0300-5038

    Fingerprint

    Cytochrome P-450 CYP2D6
    Cytochrome P-450 Enzyme System
    Genetic Polymorphisms
    Static Electricity
    Gene Frequency
    Aspartic Acid
    Pharmaceutical Preparations
    Parkinson Disease
    Catalytic Domain
    Proteins
    Nitrogen
    Alleles
    Genotype
    Pharmacology
    Polymerase Chain Reaction

    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).
    Wolf, C R ; Smith, G. / Cytochrome P450 CYP2D6. Metabolic Polymorphisms and Susceptibility to Cancer. Vol. 148 1999. pp. 209-29 (IARC Scientific Publications).
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    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.",
    author = "Wolf, {C R} and G Smith",
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    language = "English",
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    Wolf, CR & Smith, G 1999, Cytochrome P450 CYP2D6. in Metabolic Polymorphisms and Susceptibility to Cancer. vol. 148, IARC Scientific Publications, pp. 209-29.

    Cytochrome P450 CYP2D6. / Wolf, C R; Smith, G.

    Metabolic Polymorphisms and Susceptibility to Cancer. Vol. 148 1999. p. 209-29 (IARC Scientific Publications).

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

    TY - CHAP

    T1 - Cytochrome P450 CYP2D6

    AU - Wolf, C R

    AU - Smith, G

    PY - 1999

    Y1 - 1999

    N2 - 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.

    AB - 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.

    M3 - Chapter (peer-reviewed)

    SN - 978-92-832-2148-7

    VL - 148

    T3 - IARC Scientific Publications

    SP - 209

    EP - 229

    BT - Metabolic Polymorphisms and Susceptibility to Cancer

    ER -

    Wolf CR, Smith G. Cytochrome P450 CYP2D6. In Metabolic Polymorphisms and Susceptibility to Cancer. Vol. 148. 1999. p. 209-29. (IARC Scientific Publications).