Cytochrome P450 2D6/2C19 Genotyping

CPT: 81225; 81226
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Synonyms

  • DME Genotyping

Expected Turnaround Time

6 - 10 days


Related Documents


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; clotted whole blood; hemolysis; quantity not sufficient for analysis; improper container


Test Details


Use

The xTAG® CYP2D6 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 CYP2D6 gene product. CYP2D6 is involved in the metabolism of more than 65 commonly used drugs including β-blockers, antipsychotics, antidepressants, analgesics, and antiarrythmics. The CYP2D6 gene is highly polymorphic. Many alleles of 2D6 encode enzymes that have reduced or no function compared to the wild-type enzyme. Individuals can also have gene rearrangements with more than two copies of the CYP2D6 gene (gene duplication) or absence of both copies (gene deletion). Depending on the combination of alleles in an individual, drug-metabolizing phenotypes associated with the CYP2D6 enzyme can vary.

The XTAG® CYP2C19 Kit v3 is a qualitative genotyping assay, which can be used as an aid to clinicians in determining therapeutic stattegy 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

These kits are not indicated for stand-alone diagnostic purposes. These tests are not intended to be used to predict drug response or non-response. Only alleles listed will be identified by these products. Other CYP2D6 or CYP2C19 alleles, which are rare, or were unknown at the time of release of these products, will not be identified by these products. These other alleles may result in either a *1 call, a no-call, or a call of a genetically related allele included in these kits. The physiological effect of phenotype depends on individual clinical profile. The co-administration of drugs metabolized, or other drugs that can act as inducers or inhibitors, also affects the drug metabolizing phenotype.


Methodology

This assay utilizes the Luminex xTAG® CYP2D6 Kit v3 US-IVD and the Luminex xTAG® CYP2C19 Kit v3 US-IVD.

The xTAG® CYP2D6 Kit v3 is a device used to simultaneously detect and identify a panel of nucleotide varients found within the highly polymorphic CYP2D6 gene located on chromosome 22 from genomic DNA extracted from EDTA and citrate anticoagulated whole blood samples. This kit can also identify gene rearrangements associated with the deletion (*5) and duplication genotypes. The xTAG® CYP2D6 Kit v3 incorporates multiplex Polymerase Chain Reaction (PCR) and multiplex Allele Specific Primer Extension (ASPE) with Luminex's proprietary Universal Tag sorting system on the Luminex® 100/200™ xMAP® platform.

Alleles detected by the xTAG® CYP2D6 Kit v3: *1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *29, *35, *41, and DUP (duplication). The *1 allele is the most common allele in all ethnicities.

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

The combination of alleles contributes to the individual's phenotype. Drug-metabolizing phenotypes have been classified into groups, from the lowest level of metabolism to the highest level of metabolism: poor metabolizers (PMs), intermediate metabolizers (IMs), normal/extensive metabolizers (NMs/EMs), rapid metabolizers (RMs), and Ultra-rapid extesive metabolizers (UMs).

Variations in enzyme activity can lead to a variety of problems in clinical practice. PMs develop a higher serum concentration of drug, which may lead to increased risk of concentration-dependent side effects. They may also experience drug toxicity or other adverse drug reactions, or prolonged therapeutic effect because of impaired clearance of drug. If a drug is administered as a pro-drug that requires biotransformation to an active form, PMs may experience inadequate therapeutic effect if the drug does not reach the therapeutic dose. IMs may experience some of these same problems to a lesser extent. 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 pro-drugs, UMs may be at higher risk of adverse drug reactions and side effects.


References

Caudle KE, Dunnenberger HM, Freimuth RR, et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implimentation Consortium (CPIC). Genet Med. 2017 Feb;19(2):215-223.27441996
Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther. 1994 Jul;270(1):414-423.8035341
Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med. 2005 May 26;352(21):2211-2221.15917386
xTAG® CYP2D6 Kit v3 US-IVD [package insert]. Luminex; MLD-030-KPI-001 Rev G; 2018.
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
511905 Cytochrome P450 2D6/2C19 504202 2D6 Genotype: 40425-1
511905 Cytochrome P450 2D6/2C19 504376 Interpretation: 72880-8
511905 Cytochrome P450 2D6/2C19 504377 CYP2D6 Information: 49549-9
511905 Cytochrome P450 2D6/2C19 504631 Director Review: 69426-5
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 504433 Interpretation: 72879-0
511905 Cytochrome P450 2D6/2C19 504434 CYP2C19 Information: 49549-9
511905 Cytochrome P450 2D6/2C19 504632 Director Review: 69426-5
511905 Cytochrome P450 2D6/2C19 000000 MGRM Informed Consent Review N/A

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