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Test ID: 3A4V Cytochrome P450 3A4 Genotype


Advisory Information


Testing is available as the single gene assay (this test) or as a part of a focused pharmacogenomics panel, which includes testing for the following genes: CYPs 1A2, 2C9, 2C19, 2D6, 3A4, 3A5, 4F2, SLCO1B1, and VKORC1. Order PGXFP / Focused Pharmacogenomics Panel if multiple pharmacogenomic genotype testing is desired.

Specimen Required


Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Genotype Test List in Special Instructions for a list of tests that can be ordered together.

 

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 specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

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: One swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient

 

Specimen Type: DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 50 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated


Forms

1. 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 (T576) is available in Special Instructions.

2. If not ordering electronically, complete, print, and send a Pharmacogenomics Test Request Form (T797) with the specimen (https://www.mayomedicallaboratories.com/it-mmfiles/pharmacogenomics-test-request-form-mc0767-15.pdf)

Useful For

Aids in determining therapeutic strategies for drugs that are metabolized by CYP3A4, including atorvastatin, simvastatin, and lovastatin

Method Name

Polymerase Chain Reaction (PCR) With Allelic Discrimination Analysis

Reporting Name

CYP3A4 Genotype

Specimen Type

Varies

Specimen Minimum Volume

Blood: 0.4 mL
Saliva: 1 swab

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 CYP3A 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) It should also be noted that 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 3A5V / CYP3A5 Genotype.

 

One variant, CYP3A4*22 (c.522-191C>T), has been studied extensively. This variant affects hepatic expression of CYP3A4 and response to statin drugs. The CYP3A4*22 allele is associated with reduced CYP3A4 activity, which may result in a better response to lipid-lowering drugs, such as simvastatin, atorvastatin, or lovastatin. However, reduced CYP3A4 activity may also be associated with statin-induced myopathy, especially for simvastatin. Studies show that in livers with the wild-type genotype (homozygous C or CC) the CYP3A4 mRNA level and enzyme activity were 1.7- and 2.5-fold greater than in heterozygous CYP3A4*22 (CT) and homozygous CYP3A4*22 (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.(2) 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 is 5% to 8% in Caucasians 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

Effect on Enzyme Activity

*1

None (wild type)

Normal activity

*8

389G->A

No activity

*11

1088C->T

Reduced activity

*12

1117C->T

Reduced activity

*13

1247C->T

No activity

*16

554C->G

Minimal activity

*17

566T->C

No activity

*18

878T->C

Reduced activity

*22

522-191C->T

Reduced activity

*26

802C->T

No activity

Reference Values

An interpretive report will be provided.

Interpretation

An interpretive report will be provided.

 

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 RV: Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999;486:487-491

2. 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

3. Pharmacogene Variation Consortium database. Accessed 04/27/2018. Available at https://www.pharmvar.org/gene/CYP3A4

4. Lamba JK, Lin YS, Schuetz EG, Thummel KE: Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002;18:1271-1294

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

6. 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

7. Clinical Pharmacogenetic Implementation Committee Gene-Drug Table. Accessed 5/3/2017. Available at https://cpicpgx.org/genes-drugs/

Day(s) and Time(s) Performed

Monday through Friday; 8 a.m.

Analytic Time

3 days (Not reported Saturday or Sunday)

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81230-CYP3A4

LOINC Code Information

Test ID Test Order Name Order LOINC Value
3A4V CYP3A4 Genotype In Process

 

Result ID Test Result Name Result LOINC Value
BA0118 CYP3A4 Genotype 81139-8
BA0119 CYP3A4 Phenotype 53040-2
BA0120 Interpretation 69047-9
BA0121 Additional Information 48767-8
BA0197 Method 49549-9
BA0198 Disclaimer 62364-5
BA0122 Reviewed by 18771-6
Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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