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Test ID: 2C9B Cytochrome P450 2C9 Genotype by Sequence Analysis, Blood

Useful For

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

Reporting Name

CYP2C9 Genotype, B

Specimen Type

Whole Blood EDTA


Specimen Required


Multiple whole blood EDTA 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

1 mL

Specimen Stability Information

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

Clinical Information

Primary metabolism of many drugs is performed by cytochrome P450 (CYP450), a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues including 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)

Extensive metabolizer (normal)

*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

 

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.

Interpretation

A report will be provided that includes CYP2C9 genotype, predicted CYP2C9 phenotype, and assay information.

 

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)

 

Novel variants will be classified based on known, predicted, or possible effect on gene function and reported with interpretive comments detailing their potential or known significance.

 

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.

 

Drug-drug interactions and drug/metabolite inhibition must be considered in the case of intermediate metabolism.

 

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 9/21/15. Available at www.cypalleles.ki.se/cyp1a2.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, Thursday; 8 a.m.

Analytic Time

5 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-CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (eg, drug metabolism), gene analysis, common variants (eg, *2, *3, *5, *6)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
2C9B CYP2C9 Genotype, B 46724-1

 

Result ID Test Result Name Result LOINC Value
36442 CYP2C9 Phenotype 79716-7
36443 CYP2C9 Star Alleles 46724-1
36444 CYP2C9 Interpretation 69047-9
36445 Reviewed By No LOINC Needed

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reference Values

An interpretive report will be provided.

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

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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