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- DME Genotyping
This testing can assist with customizing drug therapy by providing metabolic activity information that may explain patient drug responses relevant to CYP2D6 and CYP2C19 genetic variability. These cytochrome P450 (CYP450) enzymes metabolize many drugs. Individual genetic differences of cytochrome P450 activity can result in the total absence of metabolism to ultrafast metabolism of certain drugs.
This assay does not detect other variants in the CYP2D6 or CYP2C19 genes that may affect metabolic activity.
The metabolism of drugs is also influenced by ethnicity, diet, and other medications. All factors should be considered prior to initiating new therapy. This testing does not rule out the possibility of variant alleles in other drug metabolism pathways.
DNA analysis of the Cytochrome P450 2D6 gene (OMIM 124030) and Cytochrome P450 2C19 gene (OMIM 124020, 10q24.1-10q24.3) is performed using primer extension chemistry. Multiplex PCR amplifies DNA fragments containing the variants below. Primer extension then generates a biotin-labeled product to permit flow-sorted detection of both normal and variant sequences. Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur.
Alleles detected for CYP2D6: *1,*2,*3,*4,*5,*6,*7,*8,*9,*10,*11,*15,*29,*35,*41, and gene duplications.
Variant *5 is a gene deletion. Copy number of duplicated alleles is not determined. Duplications are often functional (whole gene) but may be nonfunctional (partial gene). It is not always possible to determine which allele is duplicated.
Alleles detected for CYP2C19: *1,*2,*3,*17
*1 represents detection of the normal sequence for the variant sites tested.
Common drugs metabolized by 2D6 include, but are not limited to:
Beta-blockers: Carvedilol, s-metoprolol, propafenone, propranolol, timolol
Cardioreactive drugs: Encainide, flecainide, lidocaine, mexiletine, perhexiline
Antidepressants: Amitriptyline, clomipramine, desipramine, doxepin (E-isomers), fluoxetine, fluvoxamine, imipramine, maprotiline, nortriptyline, paroxetine, sertraline, venlafaxine
Antipsychotics: Aripiprazole, haloperidol, perphenazine, risperidone, thioridazine, zuclopenthixol
Others: Codeine, ondansetron, phenformin, tamoxifen, tramadol
Common drugs metabolized by 2C19 include, but are not limited to:
Platelet aggregation inhibitor: Clopidogrel
Poor metabolizers (PM) and intermediate metabolizers (IM) are at risk for recurrence of cardiovascular atherosclerotic disease. Alternative antiplatelet agents are recommended for PM patients and may be considered for IM patients, if not clinically contraindicated. Ultrarapid metabolizers (UM) may have an enhanced response to clopidogrel, and may be at an increased risk of bleeding. Standard dosing may be considered for UM patients. Coadministration of clopidogrel alongside CYP2C19 inhibitors such as omeprazole, esomeprazole, lansoprazole, felbamate, fluvoxamine, oral contraceptives, and voriconazole can reduce clopidogrel's platelet inhibition.
Tricyclic antidepressants (TCA): Amitriptyline, nortriptyline
Important Interactions: Studies suggest that PMs may benefit from a lower starting dose.
Selective serotonin reuptake inhibitor (SSRI): Citalopram, sertraline
Important Interactions: Mean clearance rates may be decreased in PMs as compared with EMs. Studies suggest that PMs may be at risk for SSRI related cardiotoxicity.
Proton pump inhibitors: Omeprazole
Important Interactions: Data suggests improved cure rates for EM and PM with double or triple therapy.
Antiepileptics: Diazepam, phenytoin
Important Interactions: Diazepam half-life is significantly prolonged in 2C19 PM and may cause prolonged sedation, particularly if administered with inhibitors of 2C19.
Whole blood or LabCorp buccal swab kit (Buccal swab kit contains instructions for the use of a buccal swab, PeopleSoft N° 3177.)
7 mL whole blood or LabCorp buccal swab kit
3 mL whole blood or two buccal swabs
Maintain specimen at room temperature or refrigerate at 4°C.
Causes for Rejection
Frozen specimen; clotted whole blood; hemolysis; quantity not sufficient for analysis; one buccal swab; improper container; wet buccal swab