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Cytochrome P450 Pain Management Panel, CYP2D6, CYP2C9, CYP2C19 - Common Variants (INACTIVE as of 07/05/16: Refer to 2013098)
2008920
Ordering Recommendation
May aid in drug selection and dose planning for drugs metabolized by CYP2D6, CYP2C9, and CYP2C19. Single gene tests for CYP2D6, CYP2C9, and CYP2C19 are available separately.
Mnemonic
PAIN PGX
Methodology
Polymerase Chain Reaction/Primer Extension (CYP2D6)
Polymerase Chain Reaction/Fluorescence Monitoring (CYP2C9, CYP2C19)
Performed
Mon, Thu
Reported
5-10 days
New York DOH Approval Status
This test is New York DOH approved.
Submit With Order
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
Plasma or serum. Heparinized specimens.  
Remarks
 
Stability
Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month  
Reference Interval
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 co-dominant.
Cause:
CYP2D6 gene variants.
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), *29 (1659G>A) *41 (2988G>A).
Non-functional:
*3 (2549delA), *4 (1846G>A), *5 (gene deletion),*6 (1707delT), *7 (2935A>C), *8 (1758G>T), *12 (124G>A), *14 (1758G>A).
Increased function:
Duplicated functional alleles.
Negative:
No mutations detected is predictive of *1 functional alleles.
Incidence of Poor Metabolizer Phenotype:
10 percent of Caucasians and Hispanics, 2 percent of African Americans, and 1 percent of Asians.
Clinical Sensitivity:
Drug-dependent.
Methodology:
Multiplex polymerase chain reaction anddetectionprimer extension.
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 CYP2C9 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.

Background Information for Cytochrome P450 2C9, CYP2C9, 2 Variants:
Characteristics:
The cytochrome P450 (CYP) isozyme 2C9 is involved in the metabolism of many drugs such as warfarin, phenytoin, tolbutamide, glipizide, ibuprofen, and phenobarbital. Variants of CYP2C9 will influence pharmacokinetics of CYP2C9 substrates, and may predict non-standard dose requirements.
Inheritance:
Autosomal co-dominant.
Cause:
CYP2C9 gene variants result in decreased or complete deficiency in enzyme activity.
Variants Tested:

(
Variants are numbered according to NM_000771 transcript)
Decreased function:
*2 (rs1799853, c.430C>T).
Non-functional: *3 (rs1057910, c.1075A>C).
Negative:
No variants detected is predictive of *1 functional alleles and normal enzymatic activity.
Allele Frequencies:

CYP2C9 *2: Caucasians 13 percent, Asians less than 1 percent, African Americans 3 percent.
CYP2C9 *3: Caucasians 7 percent, Asians 4 percent, African Americans 2 percent.
Clinical Sensitivity:
Drug-dependent.
Methodology:
Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity:
Greater than 99 percent.
Limitations:
Only the targeted CYP2C9 variants will be detected by this panel. Diagnostic errors can occur due to rare sequence variations. Risk of therapeutic failure or adverse reactions with CYP2C9 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.

Background Information for Cytochrome P450 2C19, CYP2C19, 9 Variants:
Characteristics:
The cytochrome P450 (CYP) isozyme 2C19 is involved in the metabolism of many drugs such as clopidogrel, phenytoin, diazepam, R-warfarin, tamoxifen, some antidepressants, proton pump inhibitors, and antimalarials. Variants of CYP2C19 will influence pharmacokinetics of CYP2C19 substrates, and may predict non-standard dose requirements.
Inheritance:
Autosomal co-dominant.
Cause:
CYP2C19 gene variants result in increased, decreased, or complete deficiency in enzyme activity.
Variants Tested: (
Variants are numbered according to NM_000769 transcript).
Decreased function: *9 (rs17884712, c.431G>A); *10 (rs6413438, c.680C>T).
Non-functional: *2 (rs4244285, c.681G>A), *3 (rs4986893, c.636G>A), *4 (rs28399504, c.1A>G), *6 (rs72552267, c.395G>A), *7 (rs72558186, c.819+2T>A), *8 (rs41291556, c.358T>C).
Increased function: *17 (rs12248560, c.-806C>T).
Negative:
No variants detected is predictive of *1 functional alleles and normal enzymatic activity.
Allele frequencies:
CYP2C19*2: African American 18.3 percent, Caucasian 14.6 percent, Middle Eastern 13.2 percent, Oceanian 54.9 percent, South Asian 34.4 percent
CYP2C19*3: African American 0.3 percent, Caucasian 0.6 percent, Middle Eastern 2.6 percent, Oceanian 13.9 percent, East Asian 8.5 percent
CYP2C19*17: African American 19.4 percent, Caucasian 21.5 percent, Oceanian 2.5 percent, South Asian 16.5 percent
Other alleles are rare, with allele frequencies of less than 1 percent in all populations studied.
Clinical Sensitivity:
Drug-dependent.
Methodology
: Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity
: Greater than 99 percent.
Limitations
: Only the targeted CYP2C19 variants will be detected by this panel. Diagnostic errors can occur due to rare sequence variations. Risk of therapeutic failure or adverse reactions with CYP2C19 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.
Note
CPT Code(s)
81226 (CYP2D6), 81225 (CYP2C19), 81227 (CYP2C9)
Components
Component Test Code*Component Chart NameLOINC
2008921Pain Management Panel, Specimen
2008925CYP2D6 Genotype
2008926CYP2D6 Phenotype
2008930CYP2C9 Genotype
2008931CYP2C9 Phenotype
2008935CYP2C19 Genotype57132-3
2008936CYP2C19 Phenotype72879-0
* 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
  • CYP2C19
  • CYP2C9
  • CYP2D6