- Patient Preparation
- Whole Blood: Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B)
Saliva: Collection Device by DNA Genotek (OCD-100, ARUP Supply #49295) 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.
- Whole Blood: Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month
Saliva: Ambient: 2 weeks; Refrigerated: Unacceptable; Frozen: Unacceptable
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.
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. Also, a combination of the *5 (gene deletion) and a gene duplication cannot be specifically identified. This combination is not expected to adversely affect the prediction of activity score or phenotype. 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.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
- Antiestrogen metabolism
- CYP2D6 drug metabolism
- P450 Genotyping
- Tamoxifin Drug Metabolism