Cytochrome P450 2D6/2C19 Genotyping

CPT: 81225; 81226
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Test Details

Synonyms

  • DME Genotyping

Use

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.

Limitations

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.

Methodology

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.

Additional Information

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.

Specimen Requirements

Specimen

Whole blood or LabCorp buccal swab kit (Buccal swab kit contains instructions for the use of a buccal swab, PeopleSoft N° 3177.)

Volume

7 mL whole blood or LabCorp buccal swab kit

Minimum Volume

3 mL whole blood or two buccal swabs

Container

Lavender-top (EDTA) tube, yellow-top (ACD) tube, or LabCorp buccal swab kit

Storage Instructions

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

Clinical Information

References

Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for cytochrome P450 2D6 genotype and codeine therapy:2014 update. Clin Pharmacol Ther. 2014 Apr;95(4):376-382.24458010
Hicks JK, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther. 2013 May;93(5):402-408.21585291
Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015 Aug;98(2):127-134.25974703
LabCorp Pharmacogenetic Testing flyer (L14582). Available upon request.
Scott SA, Sangkuhl K, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 Update. Clin Pharmacol Ther. 2013 Sep;94(3):317-323.23698643
Sibbing D, Koch W, Gebhard D, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation. 2010 Feb 2;121(4):512-518.20083681
Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 Jan 22;360(4):363-75.19106083

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
511905 Cytochrome P450 2D6/2C19 504202 2D6 Genotype: 40425-1
511905 Cytochrome P450 2D6/2C19 504203 2D6 Metabolic Activity: 79715-9
511905 Cytochrome P450 2D6/2C19 504204 2C19 Genotype: 57132-3
511905 Cytochrome P450 2D6/2C19 504205 2C19 Metabolic Activity: 79714-2
511905 Cytochrome P450 2D6/2C19 504421 Interpretation: 51971-0
511905 Cytochrome P450 2D6/2C19 504422 CYP2D6/2C19 Information: 49549-9
511905 Cytochrome P450 2D6/2C19 504423 Cytochrome P450 2D6/2C19 N/A

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