Cytochrome P450 2D6 (CYP2D6) 14 Variants and Gene Duplication
0051232
 
Ordering Recommendation
May aid in dose planning for tamoxifen and other drugs metabolized by CYP2D6.
Mnemonic
CYP 2D6
Methodology
Polymerase Chain Reaction/Primer Extension
Performed
Mon, Thu
Reported
7-14 days
New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).  
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL)  
Storage/Transport Temperature
Refrigerated.  
Unacceptable Conditions
 
Remarks
 
Stability
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
By report
Interpretive Data
Background Information for Cytochrome P450 2D6 (CYP2D6) 14 Variants and Gene Duplication:
Characteristics:
Impaired drug metabolism causing adverse drug reactions or lack of drug response. Drugs metabolized by CYP2D6 include antiestrogens (tamoxifen), alpha-blockers, analgesics, anticonvulsives, antidepressants, antidiabetics, antihypertensives, antipsychotics, antitussives, beta blockers, cardioactives, norepinephrine reuptake inhibitors, and stimulants. Additionally, many drugs inhibit CYP2D6 activity, and may affect drug response.
Inheritance:
Autosomal recessive.
Cause:
CYP2D6 gene variants.
Negative:
No mutations detected is predictive of *1 functional alleles.
Variants Tested:

Functional:
*2 (2850C>T), *2A (-1584C>G).
Decreased function:
*9 (2613-5delAGA), *10 (100C>T), *17 (1023C>T), *29 (1659G>A) *41 (2988G>A).
Non-functional:
*3 (2549A>del), *4 (1846G>A), *5 (gene deletion),*6 (1707T>del), *7 (2935A>C), *8 (1758G>T), *12 (124G>A), *14 (1758G>A).
Increased function:
Duplicated functional alleles.
Incidence of Poor Metabolizer Phenotype:
10 percent of Caucasians and Hispanics, 2 percent of African Americans, and 1 percent of Asians.
Penetrance:
Drug dependent.
Clinical Sensitivity:
Greater than 95 percent of clinically significant CYP2D6 variants are detected in Caucasians; sensitivity is unknown in other ethnicities.
Methodology:
Multiplex polymerase chain reaction and detection primer extension.
Analytical Sensitivity and Specificity:
Greater than 99 percent for the variants tested.
Limitations:
Only the targeted CYP2D6 variants will be detected. Variants in other genes will not be detected. Diagnostic errors can occur due to rare sequence variations. Variant detection is not a substitute for therapeutic drug monitoring or other clinical monitoring.
References:
Overview of CYP's (www.anaesthestist.com); nomenclature of CYP alleles (www.cypalleles.ki.se/); drug substrates/inhibitors/inducers for CYP (http://medicine.inpui.edu/flockhart).




Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

See Compliance Statement C: www.aruplab.com/CS
Note
CPT Code(s)
81226
Components
Component Test Code*Component Chart Name
0051512CYP2D6 Predicted Phenotype
0051513CYP2D6 Variant
0051514CYP2D6 Variant
0051515CYP2D6 Variant
0051516CYP2D6 Variant
2001304CYP 2D6 Specimen
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, contact interface support at interface.support@aruplab.com.
Cross References
  • Cytochrome P450 2D6 Genotype for Tamoxifen Hormonal Therapy, Saliva
  • Tamoxifin Drug Metabolism (<TestName> Cytochrome P450 2D6 (CYP2D6) 14 Mutations & Gene Duplication)