CYP2D6

Methodology: 
Multiplex polymerase chain reaction (PCR) and multiplex allele-specific primer extension (ASPE) with Luminex’s proprietary Universal Tag sorting system on the Luminex® 200™ xMAP® platform
Performed: 
Weekly
Reported: 
Within 7 - 10 days
Use: 

This test is used to dermine the CYP2D6 genotype of patients being considered for treatment with medications metabolized by CYP2D6.

Specimen Requirements: 

Whole blood or buccal swabs

Specimen preparation:
  • Blood: Transport 3 mL of whole blood collected in EDTA (lavender-top) tube (minimum 1 mL).
     
  • Buccal swab: Cells collected from the inside of the patient's cheek are needed for testing. Patients must not eat within 30 minutes of cell collection. This is the MOST IMPORTANT STEP and should be performed carefully to collect a sufficient amount of material for the analysis. For breastfeeding infants, collect specimens at least one hour after feeding. Poor specimen collection will require re-collection.
  1. Open the brush packet and remove the brush. The packet must be opened according to the instructions on top of the flap.
  2. Scrape the inside of the cheek wall horizontally 10 times in a back-and-forth motion, as you rotate the brush. 
  3. After collecting the cheek cells, place the brush directly into the correctly labeled envelope.
  4. Ensure that all the specimens are clearly and appropriately labeled.
  5. Close and seal the envelope after all specimens are collected. 
  6. Place all specimen envelopes into a 4°C storage area for pickup and delivery to University of Florida Health Pathology Laboratories.
Unacceptable conditions
  • Severely hemolyzed, clotted and/or frozen blood specimens
  • Specimens in heparin (green-top) tubes
  • Buccal swabs of insufficient quantity
Storage/Transport temperature:
  • Refrigerated
Stability (collection to shipping of the sample):
  • Ambient: 24 hours
  • Refrigerated: 1 week
  • Frozen: Unacceptable
Reference Values: 
No allelic variants detected (*1/*1)
Interpretation Data: 

Analytical interpretation: The assay will detect the following genotypes: *1, *2, *3, *4, *5, *6, *7, *8, *9, *10 *11, *15, *17, *29, *35, *41.

Alleles detected
  • Active alleles: *1, *2
  • Partially active alleles: *9, *10, *17, *29, *41
  • Inactive alleles: *3, *4, *5 (deletion), *6, *7, *8, *11, *12, *14, *15
  • Gene duplication

This test can also identify gene rearrangements associated with the deletion (*5) and duplication genotypes. The phenotype calls are based on Clinical Pharmacogenetics Implementation Consortium Guidelines (Crews KR et al., Clin Pharmacol Ther., 2014; 95: 376-82).

Based on the patient genotype one of the resulting phenotypes and interpretations will also be included on the report.

  • Resulting phenotype: Extensive metabolizer
    • Interpretation: This result predicts that this individual has an extensive (normal) metabolizer phenotype and can be treated with a recommended dose. 
       
  • Resulting phenotype: Poor metabolizer
    • Interpretation:This result predicts that this individual has a poor metabolizer phenotype and may require alternate drugs.
       
  • Resulting phenotype: Intermediate metabolizer 
    • Interpretation: This result predicts that this individual has an intermediate metabolizer phenotype and may be treated with a standard drug dose. 

      Note: CYP2D6 inhibitors may decrease the drug’s efficacy. 
       
  • Resulting phenotype: Ultra-rapid metabolizer
    • Interpretation: This result predicts that this individual has the ultra-rapid metabolizer phenotype and may require alternate drugs. 
       
  • Resulting phenotype: Extensive-to-ultra-rapid-metabolizer
    • Interpretation: The effect of the genotype on enzyme activity could not be fully determined. The resulting phenotype could be an extensive-to-ultra-rapid metabolizer depending on the number of copies of each allele. More extensive testing needs to be done to determine the genotype.
       
  • Resulting phenotype: Intermediate-to-extensive metabolizer
    • Interpretation: The effect of the genotype on enzyme activity is could not be fully determined. The resulting phenotype could be an intermediate or extensive metabolizer, depending on the number of copies of each allele. More extensive testing needs to be done to determine the genotype.
       
  • Resulting phenotype: Inconclusive
    • Interpretation: The analysis failed to yield an informative result; thus, no genotype was reported.  It cannot be determined with certainty if this is related to the specimen (degradation of substrate DNA, presence of an inhibitor substance) or reflects a mutation at the primer binding site. If clinically warranted, repeat testing on a second specimen may be of value.
       
  • Assay limitations: In the case of rare alleles that the xTAG CYP2D6 Kit v3 is not designed to detect, TDAS CYP2D6 will default to a *1, no-call, or an allele that is most genetically similar. Only alleles listed in the Methodology section will be identified by this product. Other CYP2D6 alleles, which are rare, or were unknown at the time of release of this product, will not be identified by this product. These other CYP2D6 alleles may result in either a *1 call, a no-call, or a call of a genetically related allele included in this test. A *1 call or the call of a genetically related allele may result in a phenotype prediction that is different from the phenotype prediction that would be made if the presence of the rare allele was known. As with any hybridization-based assay, underlying polymorphisms or mutations in primer-binding regions can affect the alleles being probed, and, subsequently, the calls made. The sensitivity and specificity of this assay is more than 99 percent.
Notes: 

UFHPL Test #: 10071

Test Directory