Test Catalog

Test Id : 2C9QT

Cytochrome P450 2C9 Genotype, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

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

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

CYP2C9 Genotype, V

Aliases
Lists additional common names for a test, as an aid in searching

2C9

CYP2C9

Cytochrome P450 2C9 Genotyping

Phenytoin

Siponimod

Mayzent

celecoxib

flurbiprofen

meloxicam

piroxicam

tenoxicam

Specimen Type
Describes the specimen type validated for testing

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.

 

If multiple pharmacogenomic genotype testing is needed, order PGXQP / Focused Pharmacogenomics Panel, Varies.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Genotype Test List 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 whole blood specimen in original tube. Do not aliquot.

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. Provide concentration of DNA and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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:

-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)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 0.4 mL

Saliva, extracted DNA: see Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 CYP 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:

 

Table. Enzyme Activity of Individual Star Alleles

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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

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. 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.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Rare variants may be present that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings (phenotype), additional testing should be considered.

 

Samples may contain donor DNA if obtained from patients who received non-leukoreduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell transplantation, a pretransplant DNA specimen is recommended for testing.

 

CYP2C9 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's CYP2C9 status.

 

This method may not detect all variants that result in altered CYP2C9 activity. Therefore, absence of a detectable variant does not rule out the possibility that a patient has altered CYP2C9 metabolism due to other CYP2C9 variants that cannot be detected with this method. Furthermore, when 2 or more variants are identified, the cis-/trans- status (whether the variants are on the same or opposite chromosomes) is not always known.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Genomic DNA is extracted from whole blood or saliva. Genotyping for the CYP2C9 alleles is performed using a polymerase chain reaction (PCR)-based 5'-nuclease assay. Fluorescently labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the variant. If the detection probe is an exact match to the target DNA, the 5'-nuclease polymerase degrades the probe, the reporter dye is released from the effects of the quencher dye, and a fluorescent signal is detected. Genotypes are assigned based on the allele-specific fluorescent signals that are detected.(Instruction manual: TaqMan SNP Genotyping Assay User Guide. Applied Biosystems; Revision A.0, 01/2014)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 8 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood/Saliva: 2 weeks; Extracted DNA: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81227

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
2C9QT CYP2C9 Genotype, V 46724-1
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
610096 CYP2C9 Genotype 46724-1
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
610097 CYP2C9 Phenotype 79716-7

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
New Test 2021-06-10