- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: CYP2D6, CYP2C19, and CYP2C9 metabolic phenotypes may be predicted by genotype. Predicted phenotype may apply clinically to drug and dose selection decisions, based on whether a drug is activated or inactivated by the respective cytochrome P450 enzyme. For example, a CYP2D6 poor metabolizer should avoid opioids that require CYP2D6 for activation or inactivation. Examples of opioids that do not require CYP2D6 for activation or inactivation include buprenorphine, hydromorphone, morphine, oxymorphone, and meperidine.
The combined effect of variant CYP2D6, CYP2C19, and CYP2C9 genotypes on phenotype is not well understood. Pharmacodynamics factors, such as sensitivity of the opioid receptors, and non-genetic factors, such as drug-drug interactions, should also be considered.
Inheritance: Autosomal recessive.
Negative: No variants detected is predictive of *1 functional alleles and normal enzymatic activity.
CYP2D6 Variants Tested:
Functional: *2 (c.2850C>T), *2A (c.-1584C>G).
Decreased function: *9 (c.2613-5delAGA), *10 (c.100C>T), *17 (c.1023C>T), *29 (c.1659G>A), *41 (c.2988G>A).
Non-functional: *3 (c.2549delA), *4 (c.1846G>A), *5 (gene deletion),*6 (c.1707delT), *7 (c.2935A>C), *8 (c.1758G>T), *12 (c.124G>A), *14 (c.1758G>A).
Increased function: Duplicated functional alleles.
CYP2C9 Variants Tested:
Decreased function: *2 (c.430C>T).
Non-functional: *3 (c.1075A>C).
CYP2C19 Variants Tested:
Decreased function: *9 (c.431G>A); *10 (c.680C>T).
Non-functional: *2 (c.681G>A), *3 (c.636G>A), *4 (c.1A>G), *6 (c.395G>A), *7 (c.819+2T>A), *8 (c.358T>C).
Increased function: *17 (c.991A>G; increased gene transcription).
Penetrance: Drug dependent.
Clinical Sensitivity: In Caucasians, greater than 95 percent of CYP2D6, 90 percent of CYP2C9, and 87 percent of CYP2C19 allelic variants are detected.
Methodology: CYP2D6 and CYP2C19: multiplex polymerase chain reaction and detection primer extension. CYP2C9: multiplex polymerase chain reaction, DNA hybridization, and electrochemical detection.
Analytical Sensitivity and Specificity: Greater than 99 percent for the variants tested.
Limitations: Only the targeted CYP2D6, CYP2C9, and CYP2C19 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).
|ANALGESIC SUBSTRATES OF CYTOCHROME P450|
|Cytochrome P450 (CYP)|
|Component Test Code*||Component Chart Name|
|2008921||Pain Management Panel, Specimen|
|2008925||Pain Management Panel, CYP2D6 Genotype|
|2008926||Pain Management Panel, CYP2D6 Phenotype|
|2008930||Pain Management Panel, CYP2C9 Genotype|
|2008931||Pain Management Panel, CYP2C9 Phenotype|
|2008935||Pain Management Panel, CYP2C19 Genotype|
|2008936||Pain Management Panel, CYP2C19 Phenotype|
|2008938||Pain Management Panel, Add'l Information|