Test Id : 3A4Q
Cytochrome P450 3A4 Genotype, Varies
Useful For
Suggests clinical disorders or settings where the test may be helpful
Aids in determining therapeutic strategies for drugs that are metabolized by cytochrome P450 3A4, including quetiapine
This test is not useful for managing patients receiving fluvastatin, rosuvastatin, or pravastatin since these drugs are not metabolized appreciably by CYP3A4.
Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| CULAF | Amniotic Fluid Culture/Genetic Test | Yes | No |
| _STR1 | Comp Analysis using STR (Bill only) | No, (Bill only) | No |
| _STR2 | Add'l comp analysis w/STR (Bill Only) | No, (Bill only) | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For any cord blood specimen that is received, maternal cell contamination testing may be performed at an additional charge.
Method Name
A short description of the method used to perform the test
Polymerase Chain Reaction (PCR) With Allelic Discrimination Analysis
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
3A4
CYP3A4
Cytochrome P450 3A4 (CYP3A4) Genotyping
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For any cord blood specimen that is received, maternal cell contamination testing may be performed at an additional charge.
Specimen Type
Describes the specimen type validated for testing
Varies
Ordering Guidance
Testing is available as the single gene assay (this test) and as a part of a psychotropic or focused pharmacogenomics panel.
If multiple pharmacogenomic genotype testing is desired, order PGXQP / Focused Pharmacogenomics Panel, Varies.
If genotype testing for psychotropic medications is desired, order PSYQP / Psychotropic Pharmacogenomics Gene Panel, Varies.
Additional Testing Requirements
Most drugs metabolized by CYP3A4 are also metabolized by CYP3A5, but usually to a lesser extent, so testing of CYP3A5 may also be relevant and should be determined on a case by case basis. If CYP3A5 genotyping is needed, order 3A5Q / Cytochrome P450 3A5 Genotype, Varies.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor or a liver transplant will interfere with testing. For more information about testing patients who have received a hematopoietic stem cell or liver transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Cord blood
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send cord blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 2 Swabs
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days
Additional information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
Specimen Type: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2mL with skirted conical base
Acceptable: Matrix tube, 1 mL
Collection Instructions:
1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated
Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-Pharmacogenomics Test Request (T797)
-Cardiovascular Test Request (T724)
-Neurology Specialty Testing Client Test Request (T732)
-Therapeutics Test Request (T831)
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
See Specimen Required
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Useful For
Suggests clinical disorders or settings where the test may be helpful
Aids in determining therapeutic strategies for drugs that are metabolized by cytochrome P450 3A4, including quetiapine
This test is not useful for managing patients receiving fluvastatin, rosuvastatin, or pravastatin since these drugs are not metabolized appreciably by CYP3A4.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For any cord blood specimen that is received, maternal cell contamination testing may be performed at an additional charge.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
CYP3A4 is a member of the CYP3A family of genes located on chromosome 7. The cytochrome P450 (CYP) 3A subfamily of enzymes is responsible for the metabolism of more than 50% of medications that undergo hepatic metabolism and first-pass metabolism in intestinal epithelial cells, including some lipid-lowering drugs. The CYP3A4 enzyme activity is highly variable. Interindividual differences in enzyme expression may be due to several factors including: variable homeostatic control mechanisms, disease states that alter homeostasis, up- or down-regulation by environmental stimuli, and genetic variation.(1)
One variant, CYP3A4*22 (NM_017460.6: c.522-191C>T, rs35599367), has been studied extensively. This variant affects hepatic expression of CYP3A4 and is associated with reduced CYP3A4 activity. Studies show that in livers with the reference (wild-type) genotype (homozygous C or CC) the CYP3A4 mRNA level and enzyme activity were 1.7- and 2.5-fold greater than in CYP3A4*22 heterozygotes (CT) and homozygotes (TT), respectively. The Dutch Pharmacogenetics Working Group published a guideline related to pharmacogenomic interactions with antipsychotic medications. This guideline recommends avoiding quetiapine in favor of an alternate medication to treat depression, or a dose reduction for other indications; however, the guideline indicates that the evidence is limited. Of note, there is currently no standardized method for translation of CYP3A4 genotype to CYP3A4 phenotype, and the method used in this guideline differs slightly from that used in this genotyping test. The reported allele frequency of CYP3A4*22 is 5% to 8% in the white population and 4.3% in African American and Chinese populations.
Other alleles have not been as extensively studied in clinical trials but are expected to have similar impacts on statin metabolism and the metabolism of other drugs primarily metabolized by CYP3A4.
The following table displays the CYP3A4 variants detected by this assay, the corresponding star allele, and the effect on CYP3A4 enzyme activity. Individuals without a detectable CYP3A4 variant are designated as CYP3A4*1/*1.
| CYP3A4 allele | cDNA nucleotide change (NM_017460.5) | Effect on enzyme activity |
| *1 | None (wild type) | Normal activity |
| *8 | c.389G>A | No activity |
| *11 | c.1088C>T | Reduced activity |
| *12 | c.1117C>T | Reduced activity |
| *13 | c.1247C>T | No activity |
| *16 | c.554C>G | Minimal activity |
| *17 | c.566T>C | No activity |
| *18 | c.878T>C | Reduced activity |
| *22 | c.522-191C>T | Reduced activity |
| *26 | c.802C>T | No activity |
Genotype to phenotype predictions are based on a review of the CYP3A4 literature.
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
The interpretive report includes an overview of the findings as well as the associated clinical significance.
The genotype, with associated star alleles, is assigned using standard allelic nomenclature as published by the Pharmacogene Variation (PharmVar) Consortium.(3)
For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomics Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Rare variants may be present that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing could be considered.
Samples may contain donor DNA if obtained from patients who received non-leukocyte reduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell transplantation, a pretransplant DNA specimen is recommended for testing.
CYP3A4 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's CYP3A4 status.
This test does not detect all variants that result in altered CYP3A4 activity. Therefore, absence of a detectable variant does not rule out the possibility that a patient has altered CYP3A4 metabolism due to other CYP3A4 variants that cannot be detected with this method. Furthermore, when 2 or more variants are identified, the cis-/trans- status (whether the variants are on the same or opposite chromosomes) is not always known.
Drug-drug interactions and drug-metabolite inhibition must be considered.
Drug-metabolite inhibition can occur, resulting in inhibition of CYP3A4 catalytic activity.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286(5439):487-491. doi: 10.1126/science.286.5439.487
2. Wang D, Guo Y, Wrighton SA, Cooke GE, Sadee W. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J. 2011;11(4):274-286. doi:10.1038/tpj.2010.28
3. PharmVar: Pharmacogene Variation Consortium. Updated April 29, 2025. Accessed May 15, 2025. Available at www.pharmvar.org/
4. Lamba JK, Lin YS, Schuetz EG, Thummel KE. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev. 2002;54(10):1271-1294. doi: 10.1016/s0169-409x(02)00066-2
5. 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. doi: 10.1097/FPC.0b013e32834c6edb
6. Elens L, van Schaik RH, Panin N, et al. Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitors' dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenomics. 2011;12(10):1383-1396. doi: 10.2217/pgs.11.90
7. Clinical Pharmacogenetics Implementation Consortium (CPIC). Accessed May 15. 2025. https://cpicpgx.org/
8. Beunk L, Marga N, Bianca S, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP3A4, and CYP1A2 and antipsychotics. Eur J Hum Genet. 2024;32(3):278-285. doi:10.1038/s41431-023-01347-3
Method Description
Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood or saliva. Genotyping for the CYP3A4 alleles is performed using a polymerase chain reaction (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 variant. 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.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Monday through Friday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
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
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
81230-CYP3A4
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| 3A4Q | CYP3A4 Genotype, V | 74007-6 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 610110 | CYP3A4 Genotype | 81139-8 |
| 610111 | CYP3A4 Phenotype | 81145-5 |
| 610112 | Interpretation | 69047-9 |
| 610113 | Additional Information | 48767-8 |
| 610114 | Method | 85069-3 |
| 610115 | Disclaimer | 62364-5 |
| 610116 | Reviewed by | 18771-6 |