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    39 views2 pages

    ARUP Lab Information Sheet

    Uploaded by

    tpatel0986

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
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    of 2

    Cytochrome P450 2D6, CYP2D6

    Indications for Ordering • Intermediate metabolizer phenotype (caused by one


    no-function CYP2D6 allele with a reduced function
    • Assess genetic risk of abnormal drug metabolism for drugs CYP2D6 allele) occurs in 2-11%
    metabolized by CYP2D6 • Ultra-rapid metabolizer phenotype (caused by duplication
    • Investigate genetic causes that might contribute to a of functional CYP2D6 alleles) occurs in 1-2%, but is
    personal or family history of an adverse drug event or observed more commonly in Ethiopians and Saudi
    therapeutic failure involving a drug metabolized by Arabian populations
    CYP2D6
    Treatment issues
    Test Description • CYP2D6 is an isozyme involved in the metabolism of up to
    25% of all clinically used drugs, including
    Polymerase chain reaction/fluorescence monitoring o Antiestrogens (eg, tamoxifen)
    • Variant alleles detected – *2-10, *12, *14, *17, *29, *41
    o Antitussives (eg, codeine)
    • Gene duplication also assessed o Anticonvulsants
    Tests to Consider o Antidepressants (eg, SSRIs)
    o Antihypertensives
    Primary test o Beta receptor blockers
    Cytochrome P450 2D6 (CYP2D6) 14 Variants and Gene o Stimulants (eg, methylphenidate)
    Duplication 0051232 o Cardioactives
    • May aid in drug selection and dose planning for drugs • Some drugs are
    metabolized by CYP2D6 o Activated by the pathway (eg, codeine)
    o Inactivated by the pathway (eg, nortriptyline)
    Related tests
    • Pharmacogenetic variation may lead to inappropriate
    • Many drugs can be metabolized by alternative
    concentrations of drugs and metabolites resulting in
    cytochrome P450 (CYP) enzymes
    o Toxicity and risk for adverse drug reactions
    • Additional genotyping tests are available for CYP2C9
    o Lack of therapeutic benefit
    (2012766), CYP2C19 (2012769), and CYP3A5 (2012740) as
    • Actual metabolic phenotype is subject to
    single gene tests or in a panel (2013098)
    o Drug/drug interactions
    o Panel includes a comprehensive medication guide based
    o Clinical factors
    on the genotypes detected
    o Other nongenetic factors
    • Therapeutic drug monitoring and/or metabolic ratios may
    be useful for evaluating the pharmacokinetics of a Treatment guidelines
    particular drug, for a particular patient • The Clinical Pharmacogenetics Implementation
    o See the ARUP Laboratory Test Directory Consortium (CPIC) has published dosing guidelines for
    (www.aruplab.com/) for a list of available drug-specific CYP2D6 genotypes and
    testing o Codeine – refer to CPIC dosing guideline
    Disease Overview (www.pharmgkb.org/guideline/PA166104996)
    o Tricyclic antidepressants (eg, amitriptyline) – refer to
    Prevalence CPIC dosing guideline
    • Poor metabolizer phenotype (caused by two no-function (www.pharmgkb.org/guideline/PA166105006)
    CYP2D6 alleles) o Selective serotonin reuptake inhibitors (eg, citalopram)
    o Caucasians and Hispanics – 10% – refer to CPIC dosing guideline
    o African Americans – 2% (www.pharmgkb.org/guideline/PA166127638)
    o Asians – 1%
    Genetics
    Gene – CYP2D6
    Inheritance – autosomal codominant
    Penetrance – drug dependent

    NOVEMBER 2016 | © 2013 ARUP LABORATORIES | ARUP is a nonprofit enterprise of the University of Utah and its Department of Pathology.
    500 Chipeta Way, Salt Lake City, UT 84108 | (800) 522-2787 | (801) 583-2787 | www.aruplab.com | www.arupconsult.com
    Variants detected – see table Limitations
    • Only the targeted CYP2D6 variants will be detected
    Structure/function – located on chromosome 22
    • Diagnostic errors can occur due to rare sequence
    Test Interpretation variations
    • Risk of therapeutic failure or adverse reactions with
    Sensitivity/specificity CYP2D6 substrates may be affected by genetic and
    • Clinical sensitivity – drug dependent nongenetic factors that are not detected by this test
    • Analytical sensitivity/specificity – >99% • This result does not replace the need for therapeutic drug
    Results or clinical monitoring
    • By report • It is not always possible to identify which allele is
    • No mutations detected – predictive of *1 functional duplicated when a CYP2D6 duplication is detected
    alleles
    Allele Designation Nucleotide Change Reference Sequence Identifier Predicted Enzyme Activity
    (Numbered according to M33388 sequence)
    *2 2850C>T rs16947 Functional (normal)
    *2A -1584C>G; 2850C>T rs1080985, rs16947 Functional (normal)
    *3 2549delA rs35742686 No function
    *4 1846G>A rs3892097 No function
    *5 Gene deletion No function
    *6 1707delT rs5030655 No function
    *7 2935A>C rs5030867 No function
    *8 1758G>T rs5030865 No function
    *9 2613-5delAGA rs5030656 Decreased function
    *10 100C>T rs1065852 Decreased function
    *12 124G>A rs5030862 No function
    *14 1758G>A rs5030865 No function
    *17 1023C>T rs28371706 Decreased function
    *29 1659G>A rs59421388 Decreased function
    *41 2988G>A rs28371725 Decreased function
    Duplication of Increased function
    functional alleles

    References
    • Bernard S, Neville KA, et al. Interethnic differences in • Clinical Pharmacogenetics Implementation Consortium
    genetic polymorphisms in the U.S. Population: clinical (CPIC) guideline for CYP2D6 and codeine therapy,
    implications. The Oncologist. 2006;11(2):126-135 available along with the 2014 supplement and other
    • Clinical Pharmacogenetics Implementation Consortium relevant resources at www.pharmgkb.org
    (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and • Clinical Pharmacogenetics Implementation Consortium
    dosing of selective serotonin reuptake inhibitors, available (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and
    along with the 2015 supplement and other relevant dosing of tricyclic antidepressants, available along with
    resources at www.pharmgkb.org the 2013 supplement and other relevant resources at
    www.pharmgkb.org
    • The human cytochrome P450 (CYP) allele nomenclature
    database, available at www.cypalleles.ki.se/

    NOVEMBER 2016 | © 2013 ARUP LABORATORIES

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