Cytochrome P450 2C9 Genotype by Sequence Analysis, Blood
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Predicting metabolism status for drugs that are modified by CYP2C9
Evaluating patients for adverse drug reactions involving fluoxetine(1)
As an aid in altering dosing of antiepileptic drugs such as phenytoin(4)
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
|Test ID||Reporting Name||Available Separately||Always Performed|
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
CYP2C9 Sequence Genotype
Cytochrome P450 2C9 Genotyping
P450 2C9 Genotyping
Cytochrome P450 2C9 Genotyping
P450 2C9 Genotyping
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
This test is used for assessing CYP2C9 for polymorphisms affecting the metabolism of drugs other than warfarin/Coumadin. If requesting for the use of warfarin, order WARFP/60529 Warfarin Sensitivity Genotype which includes testing for the CYP2C9 gene and VKORC1 gene promoter.
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.
1. Bone marrow and liver transplants will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions.
2. Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
3. Cytochrome P450 Patient Education Brochure (Supply T526) is available upon request.
Forms: 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 (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Ambient (preferred)|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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, metabolizes a wide variety of drugs including warfarin and many nonsteroidal anti-inflammatory drugs. It is also partially responsible for metabolizing other drugs such as fluoxetine, fluvastatin, oral hypoglycemic drugs, and phenytoin.
CYP2C9-mediated drug metabolism is variable. Some individuals have altered CYP2C9 gene sequences that result in synthesis of enzyme devoid of catalytic activity or in enzyme with diminished catalytic activity. These individuals may metabolize various drugs at a slower rate than normal and may require dosing adjustments to prevent adverse drug reactions. However, CYP2C9 alleles with "reduced function" may metabolize different drugs at different rates, ranging from near normal to poor but the literature on this is incomplete at this time.
A number of specific polymorphisms have been found in the CYP2C9 gene that results in enzymatic deficiencies. The following information outlines the relationship between the polymorphisms detected in the assay and the effect on the enzyme activity encoded by that allele:
Effect on Enzyme Metabolism
None (wild type)
Extensive metabolizer (normal)
Individuals without inactivating polymorphisms have the phenotype of an extensive drug metabolizer and are designated as CYP2C9*1/*1. All of the identified polymorphisms are autosomal recessive. Consequently, only individuals who are homozygous or who are compound heterozygous for these polymorphisms are poor metabolizers. Individuals who are heterozygous, with 1 normal gene and 1 polymorphic gene, will have metabolism intermediate between the extensive (normal) and poor metabolizers. The CYP2C9*2 allele has greater residual activity than other alleles. Consequently, an individual homozygous for the *2 allele is predicted to be an intermediate metabolizer.
Dosing of drugs that are metabolized through CYP2C9 may require adjustment for the individual patient. Patients who are poor metabolizers may benefit by dose alteration or by being switched to other comparable drugs that are not metabolized primarily by CYP2C9. The following is a partial listing of drugs known to affect CYP2C9 activity as of the date of this report.
Drugs that undergo metabolism primarily or in part by CYP2C9:
-Angiotensin II blockers: irbesartan, losartan
-Antidepressants: amitriptyline (minor), fluoxetine (minor)
-Nonsteroidal anti-inflammatory drugs (NSAIDS): celecoxib, diclofenac, ibuprofen, naproxen, piroxicam, suprofen
-Oral hypoglycemic agents: glipizide, glimepiride, glyburide/glibenclamide, nateglinide, tolbutamide
-Miscellaneous drugs: fluvastatin, phenytoin, rosuvastatin (minor), sulfamethoxazole, tamoxifen, torsemide
-Coadministration may decrease the rate of elimination of other drugs metabolized by CYP2C9.
Drugs known to increase CYP2C9 activity:
-Rifampin, secobarbital, phenobarbital
-Coadministration of these drugs increases the concentration of CYP2C9 and increases the elimination of drugs metabolized by CYP2C9.
Drugs known to decrease CYP2C9 activity:
-Amiodarone, fluconazole, fluvastatin, fluvoxamine, isoniazid, lovastatin, phenylbutazone, sertraline, sulfamethoxazole, sulfaphenazole, teniposide, ticlopidine, voriconazole, zafirlukast.
-Coadministration will decrease the rate of metabolism of CYP2C9-metabolized drugs, increasing the possibility of toxicity, particularly in heterozygous individuals.
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.
An interpretive report will be provided.
Drug-drug interactions and drug/metabolite inhibition must be considered when dealing with heterozygous individuals and individual homozygous for the *2 allele.
Drug/metabolite inhibition can occur, resulting in inhibition of residual functional CYP2C9 catalytic activity.
Patients may also develop toxicity problems if liver and kidney function are impaired.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Direct DNA testing will not detect all the known mutations that result in decreased or inactive CYP2C9. Absence of a detectable gene mutation or polymorphism does not rule out the possibility that a patient has an intermediate or poor metabolizer phenotype.
This test detects only the specified polymorphisms. Additional findings, such as small insertions and deletions or novel mutations, will be reported if found. Other polymorphisms in the primer binding regions can affect the testing, and ultimately, the genotyping assessments made.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Llerena A, Dorado P, Berecz R, et al: Effect of CYP2D6 and CYP2C9 genotypes on fluoxetine and norfluoxetine plasma concentrations during steady-state conditions. Eur J Clin Pharmacol 2004;59:869-873
2. 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
3. Martinez C, Blanco G, Ladero JM, et al: Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br J Pharmacol 2004;141:205-208
4. Hung CC, Lin CJ, Chen CC, et al: Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Ther Drug Monit 2004;26:534-540
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. The CYP2C9 gene is amplified by PCR. The PCR product is then purified and sequenced in both directions using fluorescent dye-terminator chemistry. Sequencing products are separated on an automated sequencer and trace files analyzed for variations in the exons 3, 5 and 7 using mutation detection software and visual inspection. (Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Whole Blood: 2 weeks Extracted DNA: 2 months
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
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 Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|2C9Q||CYP2C9 Sequencing||In Process|
|32164||CYP2C9 Phenotype Interpretation||In Process|
|32165||CYP2C9 Genotype Star Alleles||46724-1|
|24181||CYP2C9 430C>T (*2)||In Process|
|24182||CYP2C9 818DelA (*6)||In Process|
|24183||CYP2C9 1075A>C (*3)||In Process|
|24184||CYP2C9 1076T>C (*4)||In Process|
|24185||CYP2C9 1080C>G (*5)||In Process|
|83652||CYP2C9 Genotype Interpretation||46724-1|
|24186||CYP2C9 Reviewed by||In Process|