Cytochrome P450 Pain Management Panel (CYP2D6, CYP2C9, CYP2C19), Common Variants
2008920
 
Ordering Recommendation
Assess genetic risk for altered cytochrome P450 (CYP) CYP2D6-, CYP2C9-, and CYP2C19-mediated drug metabolism in individuals being treated with analgesics. Single gene tests for CYP2D6, CYP2C9, and CYP2C19 are available separately. For warfarin dose planning, CYP2C9 is available with VKORC1.
Mnemonic
PAIN PGX
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
Interpretive Data
Background Information for Cytochrome P450 Pain Management Panel (CYP2D6, CYP2C9, CYP2C19), Common Variants:
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)
2C9 2C19 2D6
acetaminophen -​-​-​ -​-​-​ Inactivation
buprenorphine -​-​-​ -​-​-​ -​-​-​
codeine -​-​-​ -​-​-​ ACTIVATION
fentanyl -​-​-​ -​-​-​ Inactivation
hydrocodone -​-​-​ -​-​-​ ACTIVATION
hydromorphone -​-​-​ -​-​-​ -​-​-​
ibuprofen Inactivation -​-​-​ -​-​-​
meperidine -​-​-​ ACTIVATION -​-​-​
methadone -​-​-​ Inactivation Inactivation
morphine -​-​-​ -​-​-​ -​-​-​
naproxen Inactivation -​-​-​ -​-​-​
oxycodone -​-​-​ -​-​-​ ACTIVATION
oxymorphone -​-​-​ -​-​-​ -​-​-​
propoxyphene -​-​-​ -​-​-​ -​-​-​
tapentadol Inactivation Inactivation Inactivation
tramadol -​-​-​ -​-​-​ ACTIVATION
Note
CPT Code(s)
81225, 81226, 81227
Components
Component Test Code*Component Chart Name
2008921Pain Management Panel, Specimen
2008925Pain Management Panel, CYP2D6 Genotype
2008926Pain Management Panel, CYP2D6 Phenotype
2008930Pain Management Panel, CYP2C9 Genotype
2008931Pain Management Panel, CYP2C9 Phenotype
2008935Pain Management Panel, CYP2C19 Genotype
2008936Pain Management Panel, CYP2C19 Phenotype
2008938Pain Management Panel, Add'l Information
* 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
  • CYP2C19
  • CYP2C9
  • CYP2D6