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Cytochrome P450 2D6 (CYP2D6) 15 Variants and Gene Duplication
2014547
Ordering Recommendation

Assess genetic risk of abnormal drug metabolism for drugs metabolized by CYP2D6. May aid in drug selection and dose planning for drugs metabolized by CYP2D6.

Mnemonic
CYP2D6
Methodology
Polymerase Chain Reaction/Fluorescence Monitoring
Performed
Varies
Reported
5-10 days
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Submit With Order
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
 
Collect
Whole Blood: Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Saliva
: Collection Device by Spectrum Solutions, LLC (SS-SAL-1, ARUP Supply #52535) available online through eSupply using ARUP Connect™ or by contacting ARUP Client Services at (800) 522-2787. 
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL) OR Saliva Collection Device. 
Storage/Transport Temperature
Whole Blood: Refrigerated.
Saliva: Room temperature. 
Unacceptable Conditions
Plasma or serum. Specimens collected in sodium heparin or lithium heparin. 
Remarks
 
Stability
Whole Blood: Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month
Saliva: Ambient: 2 weeks; Refrigerated: Unacceptable; Frozen: Unacceptable 
Reference Interval
By report
Interpretive Data
Background Information for Cytochrome P450 2D6 (CYP2D6) 15 Variants and Gene Duplication:
Characteristics:
The cytochrome P450 (CYP) isozyme 2D6 is involved in the metabolism of many drugs, such as antiestrogens (tamoxifen), alpha-blockers, analgesics, anticonvulsives, antidepressants, antidiabetics, antihypertensives, antipsychotics, antitussives, beta blockers, cardioactives, norepinephrine reuptake inhibitors, and stimulants. Variants of CYP2D6 will influence pharmacokinetics of CYP2D6 substrates, and may predict non-standard dose requirements.
Inheritance:
Autosomal co-dominant.
Cause:
CYP2D6 gene variants and copy number result in increased, decreased or complete deficiency in enzyme activity.
Variants Tested:
(Variants are numbered according to M33388 sequence.)
Functional:
*2 (2850C>T), *2A (-1584C>G; 2850C>T).
Decreased function:
*9 (2613-5delAGA), *10 (100C>T), *17 (1023C>T; 2850C>T), *29 (1659G>A; 2850C>T), *41 (2988G>A; 2850C>T).
Non-functional:
*3 (2549delA), *4 (100C>T; 1846G>A), *5 (gene deletion), *6 (1707delT), *7 (2935A>C), *8 (1758G>T; 2850C>T), *12 (124G>A; 2850C>T), *14 (1758G>A; 2850C>T), *36 (a *10 carrying a CYP2D7-derived exon 9 conversion).
Increased function:
Duplicated functional alleles.
Negative:
No variants detected is predictive of *1 functional alleles and normal enzymatic activity.
Allele frequencies:
CYP2D6*2 or CYP2D6*2A: African-17.6 percent, Asian-21.2 percent, Caucasian-27.6 percent, Middle Eastern-21.7 percent, Oceanian-1.2 percent
CYP2D6*3: African-0.2 percent, Asian-0 percent, Caucasian-1.3 percent, Middle Eastern-0.1 percent, Oceanian-0.2 percent
CYP2D6*4: African-4.9 percent, Asian-4.6 percent, Caucasian-18.2 percent, Middle Eastern-7.8 percent, Oceanian-2.5 percent
CYP2D6*5: African-6.3 percent, Asian-4.3 percent, Caucasian-2.8 percent, Middle Eastern-2.3 percent, Oceanian-4.3 percent
CYP2D6*6: African-0.1 percent, Asian-0 percent, Caucasian-1.0 percent, Middle Eastern-0.6 percent, Oceanian-0 percent
CYP2D6*7: African-0 percent, Asian-0 percent, Caucasian-0.1 percent, Middle Eastern-0 percent, Oceanian-0 percent
CYP2D6*8: African-0 percent, Asian-0 percent, Caucasian-0 percent, Middle Eastern-0 percent, Oceanian-0 percent
CYP2D6*9: African-0.3 percent, Asian-0.5 percent, Caucasian-2.1 percent, Middle Eastern-0 percent, Oceanian-0 percent
CYP2D6*10: African-5.3 percent, Asian-30.2 percent, Caucasian-3.0 percent, Middle Eastern-3.5 percent, Oceanian-2.5 percent
CYP2D6*12: African-0 percent, Asian-0 percent, Caucasian-0 percent, Middle Eastern-0 percent, Oceanian-0 percent
CYP2D6*14: African-0.1 percent, Asian-0.4 percent, Caucasian-0 percent, Middle Eastern-0.2 percent, Oceanian-0 percent
CYP2D6*17: African-19.0 percent, Asian-0.1 percent, Caucasian-0.4 percent, Middle Eastern-1.6 percent, Oceanian-0.1 percent
CYP2D6*29: African-7.7 percent, Asian-0 percent, Caucasian-0.1 percent, Middle Eastern-0.8 percent, Oceanian-0 percent
CYP2D6*36: African-0.3 percent, Asian-0.7 percent, Caucasian-0 percent, Middle Eastern-0 percent, Oceanian-0 percent
CYP2D6*41: African-9.2 percent, Asian-4.9 percent, Caucasian-7.9 percent, Middle Eastern-19.9 percent, Oceanian-0.9 percent
CYP2D6xN (gene duplication): African-4.7 percent, Asian-1.6 percent, Caucasian-2.6 percent, Middle Eastern-7.1 percent, Oceanian-11.8
Clinical Sensitivity: Drug-dependent.
Methodology:
Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity:
Greater than 99 percent.
Limitations:
Only the targeted CYP2D6 variants will be detected by this panel. Diagnostic errors can occur due to rare sequence variations. Risk of therapeutic failure or adverse reactions with CYP2D6 substrates may be affected by genetic and non-genetic factors that are not detected by this test. This result does not replace the need for therapeutic drug or clinical monitoring.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Components
Component Test Code*Component Chart NameLOINC
2001304CYP2D6 Specimen31208-2
2008925CYP2D6 Genotype40425-1
2008926CYP2D6 Phenotype79715-9
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • 2D6
  • Antiestrogen metabolism
  • CYP
  • CYP2D6
  • CYP2D6 drug metabolism
  • Cytochrome
  • P450
  • P450 Genotyping
  • Tamoxifin Drug Metabolism