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HelpTest ID: 3A4Q Cytochrome P450 3A4 Genotype, 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
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.
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)
Useful For
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.
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) With Allelic Discrimination Analysis
Reporting Name
CYP3A4 Genotype, VSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | |
Clinical Information
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
An interpretive report will be provided.
Interpretation
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.
Clinical Reference
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
Day(s) Performed
Monday through Friday
Report Available
3 to 8 daysTest Classification
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
81230-CYP3A4
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| 3A4Q | CYP3A4 Genotype, V | 74007-6 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 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 |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
For any cord blood specimen that is received, maternal cell contamination testing may be performed at an additional charge.
mml-pgxsingle