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Test ID: 2C9QT Cytochrome P450 2C9 Genotype, Varies


Ordering Guidance


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

 

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 PGXQP / Focused Pharmacogenomics Panel, Varies 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) 9 days/Refrigerated 30 days

 

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: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

 

Specimen Type: Extracted 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. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Neurology Specialty Testing Client Test Request (T732)

-Therapeutics Test Request (T831)

Useful For

Identifying individuals who may be at risk for altered metabolism of drugs that are modified by cytochrome P450 2C9

Method Name

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

Reporting Name

CYP2C9 Genotype, V

Specimen Type

Varies

Specimen Minimum Volume

Blood: 0.4 mL
Saliva: 1 swab

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

Primary metabolism of many drugs is performed by the cytochrome P450 (CYP) 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

(NM_000771.3)

Effect on enzyme metabolism

*1

None (wild type)

Normal activity

*2

c.430C>T

Reduced activity

*3

c.1075A>C

No activity

*4

c.1076T>C

Reduced activity

*5

c.1080C>G

Reduced activity

*6

c.818delA

No activity

*8

c.449G>A

Reduced activity

*9

c.752A>G

Normal activity

*11

c.1003C>T

Reduced activity

*12

c.1465C>T

Reduced activity

*13

c.269C>T

No activity

*14

c.374G>A

Reduced activity

*15

c.485C>A

No activity

*16

c.895A>G

Reduced activity

*17

c.1144C>T

Reduced activity

*18

c.1190A>C

No activity

*25

c.353_362del

No activity

*26

c.389C>G

Reduced activity

*28

c.641A>T

Reduced activity

*30

c.1429G>A

Reduced activity

*33

c.395G>A

No activity

*35

c.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. Phenotyping is derived from the Pharmacogene Variation Consortium website(1), the Clinical Pharmacogenetics Implementation Consortium website (2), published guidelines (3-5), and an exhaustive review of the CYP2C9 literature (6-7). 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 Pharmacogene Variation (PharmVar) Consortium.(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. PharmVar: Pharmacogene Variation Consortium. Updated March 3, 2021. Accessed March 22, 2021. Available at www.pharmvar.org/

2. Clinical Pharmacogenetics Implementation Consortium (CPIC). Accessed October 14, 2020. Available at https://cpicpgx.org/

3. Karnes JH, Rettie AE, Somogyi AA, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update. Clin Pharmacol Ther. 2021 Feb;109(2):302-309. doi: 10.1002/cpt.2008

4. Johnson JA, Caudle KE, Gong L, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017 Sep;102(3):397-404. doi: 10.1002/cpt.668

5. Theken KN, Lee CR, Gong L, et al: Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clin Pharmacol Ther. 2020 Aug;108(2):191-200. doi: 10.1002/cpt.1830

6. Niemi M, Cascorbi I, Timm R, Kroemer HK, Neuvonen PJ, Kivisto KT: Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin Pharmacol Ther. 2002;72(3):326-332. doi: 10.1067/mcp.2002.127495

7. Blaisdell J, Jorge-Nebert LF, Coulter S, et al: Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics. 2004;14(8):527-537. doi: 10.1097/01.fpc.0000114759.08559.51

Day(s) Performed

Monday through Friday

Report Available

3 to 8 days

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 US Food and Drug Administration.

CPT Code Information

81227

LOINC Code Information

Test ID Test Order Name Order LOINC Value
2C9QT CYP2C9 Genotype, V 46724-1

 

Result ID Test Result Name Result LOINC Value
610096 CYP2C9 Genotype 46724-1
610097 CYP2C9 Phenotype 79716-7
610568 CYP2C9 Activity Score In Process
610098 Interpretation 69047-9
610099 Additional Information 48767-8
610100 Method 85069-3
610101 Disclaimer 62364-5
610102 Reviewed by 18771-6
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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