Test ID: 3A4O
Cytochrome P450 3A4 Genotype, Saliva
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
As an aid to clinicians in determining therapeutic strategies for drugs that are metabolized by CYP3A4, including atorvastatin, simvastatin and lovastatin
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Polymerase Chain Reaction (PCR) 5’-Nuclease End-Point Allelic Discrimination Analysis
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Saliva Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Collection Container/Tube: Oragene DNA Self-Collection Kit (Supply T651)
Specimen Volume: Full tube
Collection Instructions:
1. Fill tube to line.
2. Send specimen in original container per kit instructions.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Saliva | Ambient | |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The cytochrome P450 (CYP) 3A4 enzyme is responsible for the metabolism of approximately 50% of drugs that undergo hepatic metabolism and first pass metabolism in intestinal epithelial cells, including lipid-lowering drugs. The CYP3A4 enzyme activity is highly variable.(1) While polymorphisms and mutations have been described for the CYP3A4 gene, they do not explain the highly variable enzymatic activity of the encoded protein.(2) A CYP3A4 (c522-191C->T) intron 6 polymorphism (CYP3A4*22) affects hepatic expression of CYP3A4 and response to statin drugs. The CYP3A4*22 allele is associated with reduced CYP3A4 activity, resulting in a better response to lipid-lowering drugs, such as simvastatin, atorvastatin, or lovastatin. Studies show that CYP3A4 mRNA level and enzyme activity in the liver with CC genotype were 1.7- and 2.5-fold greater than in CT and TT carriers, respectively. In 235 patients taking stable doses of drugs for lipid control, carriers of the T allele required significantly lower statin doses for optimal lipid control than did non-T carriers.(3) These results indicate that CYP3A4*22 markedly affects expression of CYP3A4 and could serve as a biomarker for CYP3A4 metabolizer phenotype. The reported allele frequency of CYP3A4*22 in Caucasians was 5% to 8%. The allele frequency is 4.3% in African Americans and in Chinese.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
CC Detected:
The CYP3A4 *22 (c.522-191C->T) allele was not identified (ie, CC genotype detected) in this individual. This genotype predicts higher CYP3A4 enzyme activity. Individuals with this genotype may require higher statin doses for optimal therapy.
CT Detected:
This individual is heterozygous (CT) for the CYP3A4*22 (c.522-191C->T) allele. This genotype predicts lower CYP3A4 enzyme activity. Individuals with this genotype may require lower statin doses.
TT Detected:
This individual is homozygous (TT) for the CYP3A4*22 (c.522-191C->T) allele. This genotype predicts lower enzyme activity. Individuals with this genotype may require significantly lower statin doses.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test does not detect polymorphism or mutations other than the specific intron 6 polymorphism.
This test is not indicated for stand-alone diagnostic purposes.
This test is not intended to be used to predict drug response.
Drug-drug interactions and drug/metabolite inhibition must be considered.
Drug/metabolite inhibition can occur, resulting in inhibition of CYP3A4 catalytic activity.
Patients may also develop toxicity problems if liver and kidney function are impaired.
CYP3A4 genotyping should not be ordered for managing patients receiving fluvastatin, rosuvastatin, or pravastatin since these drugs are NOT metabolized appreciably by CYP3A4.
Saliva specimen type should be used on patients who have had blood transfusions or bone marrow transplantation. Blood transfusions or bone marrow transplantation prior to having blood drawn for DNA analysis can generate false results as DNA in the specimen may be a mix of patient and donor DNA.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing could be considered.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Evans WE, Relling RV: Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999;486:487-491
2. Lamda JK, Lin YS, Schuetz EG, Thummel KE: Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002;18:1271-1294
3. Wang D, Guo Y, Wrighton SA, et al: Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J 2011;11:274-286
4. Elens L, Becker ML, Haufroid V, et al: Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with simvastatin-mediated cholesterol reduction in the Rotterdam study. Pharmacogenet Genomics 2011;21(12):861-866
5. Elens L, Van Schaik RH, Panin N, et al: Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitor’ dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenomics 2011;12(10):1383-1396
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from saliva. Genotyping for the CYP3A4 *22 allele is performed using a PCR-based 5’-nuclease assay. Fluorescently labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the polymorphism. If the detection probe is an exact match to the target DNA, the 5’-nuclease polymerase degrades the probe, the reporter dye is released from the effects of the quencher dye, and a fluorescent signal is detected. Genotypes are assigned based on the allele-specific fluorescent signals that are detected.(Package insert: TaqMan SNP Genotyping Assay, Applied Biosystems)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81401-CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4) (eg, drug metabolism), common variants (eg, *2, *3, *4, *5, *6)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 34692 | CYP3A4 Genotype Result | N/A |
| 34693 | CYP3A4 Interpretation | N/A |
| 34694 | Reviewed by | N/A |
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