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Test ID: 3A5V CYP3A5 Genotype


Additional Testing Requirements


In general, most drugs metabolized by CYP3A5 are also metabolized by CYP3A4 and usually to a greater degree than CYP3A5. For this reason, substrates of these 2 enzymes are sometimes listed together in publications and genotyping of both genes might be needed to fully understand the metabolism of these drugs and predict phenotype. If CYP3A4 genotyping is needed, order 3A4V / Cytochrome P450 3A4 Genotype.



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: DNA Saliva Collection Kit (T786: fees apply)

Container/Tube: 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 optimizing treatment with tacrolimus and other drugs metabolized by CYP3A5

Method Name

Polymerase Chain Reaction (PCR) With Allelic Discrimination Analysis

Reporting Name

CYP3A5 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

CYP3A5 is a member of the CYP3A family of genes located on chromosome 7. The CYP3A subfamily of enzymes responsible for the metabolism of more than 50% of medications that undergo hepatic metabolism and first-pass metabolism in intestinal epithelial cells. The CYP3A5 expression level and enzymatic activity can be modulated by genetic variation. CYP3A5 allelic frequency depends upon ethnicity. For example, in individuals of European descent the most common allele is the CYP3A5*3 allele (c.219-237A>G), which results in a splicing defect and absence of enzyme activity. In individuals of African descent, the *1 allele (functional enzyme) is most common. The distribution of CYP3A5*3 allele frequencies ranges from 0.14 among sub-Saharan Africans to 0.95 in European populations.

 

In general, most drugs metabolized by CYP3A5 are also metabolized by CYP3A4 and usually to a greater degree than CYP3A5. For this reason, substrates of these 2 enzymes are sometimes listed together in publications and genotyping of both genes might be needed to fully understand the metabolism of these drugs and predict phenotype. If CYP3A4 genotyping is needed, order 3A4V / Cytochrome P450 3A4 Genotype.

 

CYP3A5 testing is commonly ordered for patients receiving tacrolimus. Tacrolimus is an immunosuppressive calcineurin inhibitor used in transplant recipients. Tacrolimus has a low therapeutic index with a wide range of side effects and large interindividual variability in its pharmacokinetics, particularly in the dose required to reach target trough blood concentrations, thus necessitating routine therapeutic drug monitoring in clinical practice.

 

Tacrolimus dose requirements are most closely associated with CYP3A5 genotype even though the drug is metabolized by both CYP3A4 and CYP3A5. According to existing literature and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, individuals with at least 1 copy of fully functional CYP3A5 (ie, *1/*1 and *1/*3) require a higher dose of tacrolimus to reach the targeted whole blood concentrations than those without a copy of a fully functional CYP3A5 allele (ie, *3/*3). CYP3A5 genotyping may predict dose requirements for tacrolimus, but does not replace the need for therapeutic monitoring to guide tacrolimus dose adjustments. For a patient with the CYP3A5*3/*3 genotype, initiating tacrolimus therapy with a standard (normal) dose is recommended. One of the complications in interpreting CYP3A5 genotyping results and the effect of genotype on drug dosing is the fact that most individuals involved in drug trials have been of European decent. Individuals of European decent are more likely to have the CYP3A5*3/*3 genotype, which predicts a poor metabolizer phenotype. Dosing requirements were derived from these clinical trials so individuals with 1 or 2 copies of CYP3A5*1, will functionally behave like rapid or ultrarapid metabolizers and may require higher doses of CYP3A5 metabolized drugs.

 

The following table displays the CYP3A5 variants detected by this assay, the corresponding star allele, and the effect on CYP3A5 enzyme activity:

 CYP3A5 Allele

cDNA Nucleotide Change

Effect on Enzyme Activity

*1

None (wild type)

Normal activity

*3

219-237A->G

No activity

*5

432+2T->C

No activity

*6

624G->A

No activity

*7

1035dup

No activity

*8

82C->T

Reduced activity

*9

1009G->A

Reduced 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 Human Cytochrome P450 (CYP) Allele Nomenclature Database Committee.(1)

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic 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. Human Cytochrome P450 (CYP) Allele Nomenclature Database. Accessed 5/3/2017. Available at www.cypalleles.ki.se/cyp3a5.htm

2. Birdwell K, Decker B, Barbrino J, et al: Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther 2015:98(1):19-24 doi: 10.1002/cpt.113

3. Thervet E, Loriot MA, Barbier S, et al: Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin Pharmacol Ther 2010;87:721-726

4. Lamba J, Hebert J, Schuetz E, et al: PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenet Genomics 2012 Jul; 22(7):555-558

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

81231-CYP3A5

LOINC Code Information

Test ID Test Order Name Order LOINC Value
3A5V CYP3A5 Genotype In Process

 

Result ID Test Result Name Result LOINC Value
BA0123 CYP3A5 Genotype In Process
BA0124 CYP3A5 Phenotype 79717-5
BA0125 Interpretation 69047-9
BA0126 Additional Information 48767-8
BA0199 Method 49549-9
BA0200 Disclaimer 62364-5
BA0127 Reviewed by In Process
Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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