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Test ID: 3A4B Cytochrome P450 3A4 Genotype, Blood

Reporting Name

CYP3A4 Genotype, B

Useful For

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

Specimen Type

Whole Blood EDTA


Specimen Required


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

 

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send specimen in original tube.


Specimen Minimum Volume

0.3 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood EDTA Ambient (preferred)
  Refrigerated 

Reference Values

An interpretive report will be provided.

Day(s) and Time(s) Performed

Monday; 8 a.m.

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

81401-CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4) (eg, drug metabolism), common variants (eg, *2, *3, *4, *5, *6)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
3A4B CYP3A4 Genotype, B In Process

 

Result ID Test Result Name Result LOINC Value
34689 CYP3A4 Genotype Result 81139-8
34690 CYP3A4 Interpretation 69047-9
34691 Reviewed by No LOINC Needed

Clinical Information

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. 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) A CYP3A4 intron 6 variant, CYP3A4*22 (c.522-191C->T), 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 in Caucasians is 5% to 8%. The allele frequency is 4.3% in African Americans and in Chinese.

 

Individuals without a detectable CYP3A4*22 variant, will have the predicted phenotype of an extensive drug metabolizer and are designated as CYP3A4*1/*1.

Interpretation

Extensive metabolizer:

The CYP3A4*22 allele was not detected. Therefore, this patient is expected to be an extensive metabolizer. Rapid metabolism of drugs that are inactivated or activated by CYP3A4 is expected. Coadministration of CYP3A4 inhibitors may increase the risk of toxicity for drugs inactivated by CYP3A4, or may cause lack of efficacy for drugs activated by CYP3A4.

 

Intermediate to extensive metabolizer:

One copy of the CYP3A4*22 allele was detected. Therefore, this patient is expected to be an intermediate to extensive metabolizer.  

Reduced metabolism of drugs that are inactivated or activated by CYP3A4 is expected when compared to patients who are *1/*1. Coadministration of CYP3A4 inhibitors may increase the risk of toxicity for drugs inactivated by CYP3A4, or may cause lack of efficacy for drugs activated by CYP3A4.

 

Intermediate metabolizer:

Two copies of the CYP3A4*22 allele were detected. Therefore, this patient is expected to be an intermediate metabolizer. Drugs that are inactivated or activated by CYP3A4 are metabolized at reduced rate when compared to patients who are *1/*1. Coadministration of CYP3A4 inhibitors may increase the risk of toxicity for drugs inactivated by CYP3A4, or may cause lack of efficacy for drugs activated by CYP3A4.

 

Absence of the *22 allele does not rule out the possibility that a patient harbors another variant that can impact the function of this enzyme, drug response, or drug side effects. The CYP3A4 genotype is only one factor that should be taken into consideration for drug dosing.

 

For additional information regarding pharmacogenomic genes and their associated drugs, please 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. Lamba JK, Lin YS, Schuetz EG, Thummel KE: Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002;18:1271-1294

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

Analytic Time

1 day (Not reported Saturday or Sunday)

Method Name

Polymerase Chain Reaction (PCR) 5’-Nuclease Endpoint Allelic Discrimination Analysis

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 1 of the following forms with the specimen:

Cardiovascular Test Request Form (T724) (http://www.mayomedicallaboratories.com/it-mmfiles/cardiovascular-request-form.pdf)

Neurology Specialty Testing Client Test Request (T732) (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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