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Cytochrome P450 Genotype Panel
2013098
Ordering Recommendation

Assess genetic risk of abnormal drug metabolism for drugs metabolized by CYP2D6, CYP2C9, CYP2C19, and CYP3A5. May aid in drug selection and dose planning for many drugs.

Mnemonic
CYP PAN
Methodology
Polymerase Chain Reaction/Fluorescence Monitoring
Performed
Mon, Thu
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
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.


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.


Background Information for Cytochrome P450 3A5 Genotyping, CYP3A5, 2 Variants:
Characteristics:
The cytochrome P450 (CYP) 3A subfamily of enzymes is involved in metabolism of many drugs such as immunosuppressants, antibiotics, antivirals, benzodiazepines, and steroids. Nonfunctional variants of CYP3A5 are common in some populations, preventing expression and function of the CYP3A5 enzyme, which will influence pharmacokinetics of CYP3A5 substrates, and may predict non-standard dose requirements.
Inheritance:
Autosomal co-dominant.
Cause:
CYP3A5 gene variants result in enzyme deficiency.
Variants Tested:
CYP3A5 non-functional alleles: *3 (rs776746, c.6986A>G), *6 (rs10264272, c.14690G>A).
Negative: No variants detected is predictive of *1 functional alleles and normal CYP3A5 enzyme activity. (Variants are numbered according to NG_007938.1 transcript)
Allele Frequencies:
CYP3A5*3: African-29.8 percent, Asian-74.2 percent, Caucasian-92.1 percent, Latin American-76.5 percent, Middle Eastern-88.1 percent.
CYP3A5*6: African-17.2 percent, Asian-0.1 percent, Caucasian-0.1 percent, Latin American-3.7 percent, Middle Eastern-1.9 percent.
CYP3A5*7: African-7.7 percent, Asian-0 percent, Caucasian-0 percent, Latin American-2.5 percent, Middle Eastern-0.2 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 CYP3A5 variants will be detected by this panel. Diagnostic errors can occur due to rare sequence variations. Many CYP3A substrates are also metabolized by CYP3A4, for which clinically relevant genetic variation is not recognized to be common. Risk of therapeutic failure or adverse reactions with CYP3A5 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)
Components
Component Test Code*Component Chart NameLOINC
2008925CYP2D6 Genotype40425-1
2008926CYP2D6 Phenotype79715-9
2008930CYP2C9 Genotype46724-1
2008931CYP2C9 Phenotype79716-7
2008935CYP2C19 Genotype57132-3
2008936CYP2C19 Phenotype79714-2
2012742CYP3A5 Genotype81140-6
2012743CYP3A5 Phenotype79717-5
2013099CYP Panel Specimen31208-2
2013229EER Cytochrome P450 Genotype Panel11526-1
* 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