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This testing can assist with customizing drug therapy by providing metabolic activity information that may explain patient drug responses relevant to CYP2C19 genetic variability. The 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 CYP2C19 gene 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 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 perform 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: *1,*2,*3,*17
*1 represents detection of the normal sequence for the variant sites tested.
Common prescription medications that may be impacted by CYP2C19 gene variants are listed below. The following list is intended as a guide and is not inclusive of all clinically relevant drugs.
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 collection kit contains instructions for 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; hemolysis; quantity not sufficient for analysis; improper container; one buccal swab; wet buccal swab