Cytochrome P450 2C19 Genotyping

CPT: 81225
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Expected Turnaround Time

5 - 10 days


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Specimen Requirements


Specimen

Whole blood


Volume

7 mL


Minimum Volume

3 mL


Container

Lavender-top (EDTA) tube or yellow-top (ACD) tube


Storage Instructions

Maintain specimen at room temperature or refrigerate at 4°C.


Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container


Test Details


Use

The xTAG® CYP2C19 Kit v3 is a qualitative genotyping assay, which can be used as an aid to clinicians in determining therapeutic strategy for the therapeutics that are metabolized by the CYP2C19 gene product. CYP2C19 is involved in the metabolism of drugs including clopidogrel, anticonvulsants, diazepam, omeprazole, tricyclic antidepressants and proton pump inhibitors. The CYP2C19 gene is highly polymorphic. Many alleles of CYP2C19 encode enzymes that have non-functional, decreased or increased enzyme activity compared to wild-type. Depending on the combination of alleles in an individual, drug-metabolizing phenotypes associated with the CYP2C19 enzyme can vary.


Limitations

The kit is not indicated for stand-alone diagnostic purposes. This test is not intended to be used to predict drug response or non-response. Only alleles listed will be identified by this product. Other CYP2C19 alleles, which are rare, or were unknown at the time of release of this product, will not be identified by this product. These other alleles may result in either a *1 call, a no-call, or a call of a genetically related allele included in this kit. The physiological effect of CYP2C19 phenotype depends on individual clinical profile. The co-administration of drugs metabolized by CYP2C19, or other drugs that can act as inducers or inhibitors of CYP2C19, also affects the drug metabolizing phenotype. Other factors include the individual's age, weight, gender, renal and liver function, disease status, and lifestyle factors such as smoking, diet and alcohol consumption. It is important to interpret genotyping test results in the context of an individual's profile.


Methodology

This assay utilizes the Luminex xTAG® CYP2C19 Kit v3 US-IVD.

The xTAG® CYP2C19 Kit v3 is an in vitro diagnostic test used to simultaneously detect and identfy a panel of nucleotide varients found within the highly polymorphic CYP450 2C19 gene, located on chromosome 10q24, from genomic DNA extracted from EDTA or citrate anticoagulated whole blood samples. The xTAG® CYP2C19 Kit v3 incorporates multiplex Polymerase Chain Reaction (PCR) and multiplex Allele Specific Primer Extension (ASPE) with a proprietary universal array system on the Luminex platform.

Alleles detected by xTAG® CYP2C19 Kit v3: *1,*2,*3,*17. The wild-type (WT) allele, CYP2C19 *1, is the most common variant.


Additional Information

Drug-metabolizing phenotypes can be classified according to the level of metabolism: poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultra-rapid metabolizers (UMs). An idividual's phenotype depends on the combination of alleles they have. PMs have little to no CYP2C19 enzyne activity and have two non-functional alleles. EMs are identified as having normal enzyme activity, and are homozygous wild-type for the *1 functional allele. UMs have increased enzyme activity resulting from two gain-of-function alleles or one functional allele and one gain-of-function allele. The *17 allele is the only UM allele identified thus far for CYP2C19. IMs have intermediate enzyme activity resulting from one functional allele and one loss-of-function allele. The consequence of a *17 allele with a loss of function allele may be in between the EM and IM phenotypes and may possibly be substrate dependent.

Variations in CYP2C19 enzyme activity can lead to a variety of clinical implications. PMs have reduced enzyme activity and may require alternative therapeutic treatment or adjustment of standard dosage regime to reduce the risk of concentration-dependent side effects, overdose drug toxicity or prolonged therapeutic effect as a result of impaired clearance of drug. If a drug is administered as a prodrug that requires activation by CYP2C19 enzyme, PMs may experience inadequate therapeutic effect if the drug does not reach the therapeutic dose. EMs in general have normal enzyme activity and can be administered CYP2C19-metabolized drugs using standard dosing. EMs who are heterozygous for a varient allele with a non-functional allele may have a modest decrease in enzyme activity. For UMs, rapid metabolism of the drug may lead to inadequate drug efficacy and therapeutic failure, because the drug may not reach the therapeutic serum concentration. For prodrugs like clopidogrel, UMs may be at risk of elevated exposure to active drug metabolites leading to adverse drug reactions.


References

Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet. 2000 Nov 11;356(9242):1667-1671.11089838
Xie HG, Zou JJ, Hu ZY, Zhang JJ, Ye F, Chen SL. Individual variability in the disposition of and response to clopidogrel: pharmacogenomics and beyond. Pharmacol Ther. 2011 Mar;129(3):267-289.20965214
xTAG® CYP2C19 Kit v3 US-IVD [package insert]. Luminex; MLD-046-KPI-001 Rev E; 2018.

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
511675 Cytochrome P450 2C19 504204 2C19 Genotype: 57132-3
511675 Cytochrome P450 2C19 504205 2C19 Metabolic Activity: 79714-2
511675 Cytochrome P450 2C19 504632 Director Review: 69426-5
511675 Cytochrome P450 2C19 504433 Interpretation: 72879-0
511675 Cytochrome P450 2C19 504434 CYP2C19 Information: 49549-9
511675 Cytochrome P450 2C19 000000 MGRM Informed Consent Review N/A

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