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Test ID: 2C9GV Cytochrome P450 2C9 Genotype


Advisory Information


If patient is or will be using warfarin, the preferred test is WARSV / Warfarin Response Genotype, which includes testing of CYP2C9, VKORC1, CYP4A2, and rs12777823.



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)

Container/Tube: Saliva Swab Collection Kit (T786: fees apply)

Specimen Volume: 1 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

Identifying individuals who may be at risk for altered metabolism of drugs that are modified by CYP2C9

Method Name

Real-Time Polymerase Chain Reaction (PCR) with Allelic Discrimination Analysis

Reporting Name

CYP2C9 Genotyping Test

Specimen Type

Varies

Specimen Minimum Volume

Blood: 0.4 mL
Saliva: 1 swab

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Clinical Information

Primary metabolism of many drugs is performed by the cytochrome P450 (CYP450) enzymes, a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues, but primarily in the intestines and liver. One of these CYP450 enzymes, CYP2C9, participates in the metabolism of a wide variety of drugs including warfarin and phenytoin.

 

CYP2C9-mediated drug metabolism is variable among individuals. Some individuals have CYP2C9 genetic variants that lead to severely diminished or absent CYP2C9 catalytic activity (ie, poor metabolizers). These individuals may metabolize various drugs at a slower rate than normal and may require dosing adjustments to prevent adverse drug reactions.

 

A number of specific CYP2C9 variants have been identified that result in enzymatic deficiencies. The following information outlines the relationship between the variants detected in the assay and their effect on enzyme activity:

 

CYP2C9 Allele

cDNA Nucleotide Change

Effect on Enzyme Metabolism

*1

None (wild type)

Normal activity

*2

430C->T

Reduced activity

*3

1075A->C

No activity

*4

1076T->C

Reduced activity

*5

1080C->G

Reduced activity

*6

818delA

No activity

*8

449G->A

Substrate specific

*9

752A->G

Reduced activity

*11

1003C->T

Reduced activity

*12

1465C->T

Reduced activity

*13

269C->T

Minimal activity

*14

374G->A

Minimal activity

*15

485C->A

No activity

*16

895A->G

Minimal activity

*17

1144C->T

Reduced activity

*18

1190A->C

No activity

*25

353_362del

No activity

*26

389C->G

Minimal activity

*28

641A->T

Minimal activity

*30

1429G->A

Minimal activity

*33

395G->A

Minimal activity

*35

374G->T + 430C->T

No activity

 

CYP2C9 drug metabolism is dependent on the specific genotype detected, and also on the number and type of drugs administered to the patient. Individuals without a detectable CYP2C9 variant will have the predicted phenotype of an extensive drug metabolizer and are designated as CYP2C9 *1/*1. If an individual is homozygous or compound heterozygous for an allele with no activity, the individual is predicted to be a poor metabolizer. If an individual is heterozygous for an allele with no activity, the individual is predicted to be an intermediate metabolizer. In some cases, a range of potential phenotypes may be given, depending on the combination of alleles identified.

 

Patients who are poor metabolizers may benefit from dose alteration or selection of a comparable drug that is not primarily metabolized by CYP2C9. It is important to interpret the results of testing in the context of other coadministered drugs.

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 Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

 

Drug-drug interactions and drug/metabolite inhibition must be considered in the case of all metabolizer categories except poor metabolizer.

 

It is important to interpret the results of testing and dose adjustments in the context of hepatic and renal function and patient age.

Clinical Reference

1. Human Cytochrome P450 (CYP) Allele Nomenclature Database. Accessed 5/3/2017. Available at www.cypalleles.ki.se/cyp2c9.htm/

2. Caudle KE, Rettie AE, Whirl-Carrillo M, et al: Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther 2014;96(5):542-548

3. Niemi M, Cascorbi I, Timm R, et al: Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin Pharmacol Ther 2002;72:326-332

4. Johnson JA, Gong L, Whirl-Carrillo M, et al: Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther 2011;90(4):625-629

5. Blaisdell J, Jorge-Nebert LF, Coulter S, et al: Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics 2004;14(8):527-537

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

81227

LOINC Code Information

Test ID Test Order Name Order LOINC Value
2C9GV CYP2C9 Genotyping Test 46724-1

 

Result ID Test Result Name Result LOINC Value
BA0108 CYP2C9 Genotype 82939-0
BA0109 CYP2C9 Phenotype 79716-7
BA0110 Interpretation 69047-9
BA0111 Additional Information 48767-8
BA0193 Method 49549-9
BA0194 Disclaimer 62364-5
BA0112 Reviewed by 18771-6
Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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