Cytochrome P450 2C19 Genotype by Sequence Analysis
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Identifying patients who are poor metabolizers or extensive metabolizers of drugs that are modified by CYP2C19
Individuals who have resistance to anticoagulation with clopidogrel
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|
|2C19||CYP2C19 Sequence Genotype||No||Yes|
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
CYP2C19 Sequence Genotype
Cytochrome P450 2C19 Genotyping
P450 2C19 Genotyping
Treatment Resistant Depression Panel
Cytochrome P450 2C19 Genotyping
P450 2C19 Genotyping
Treatment Resistant Depression Panel
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.
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, CYP2C19, metabolizes a wide variety of drugs including antiulcer drugs such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam. It is also partially responsible for metabolizing other drugs such as the beta-blocker propranolol and the antidepressants fluvoxamine and fluoxetine. It is also involved in the activation of the anticoagulant clopidogrel.
CYP2C19 drug metabolism is variable. Some individuals have altered CYP2C19 gene sequences that result in synthesis of enzyme devoid of catalytic activity or in enzyme with diminished catalytic activity. These individuals metabolize clopidogrel, mephenytoin, omeprazole, diazepam, proguanil, and propranolol poorly. A number of specific polymorphisms have been found in the CYP2C19 gene that result in enzymatic deficiencies. The frequency of these polymorphisms varies within the major ethnic groups. CYP2C19 polymorphisms that produce poor metabolizers are found with frequencies of 2% to 5% in Caucasians, 4% in African Americans, 13% to 23% in Asians, and 38% to 79% in Polynesians and Micronesians.
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)
Severely decreased activity (70%-90%)
Individuals without inactivating polymorphisms have the phenotype of an extensive drug metabolizer and are designated as CYP2C19*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.
Individuals receiving clopidogrel who are carriers (heterozygous) or homozygous for the CYP2C19 polymorphisms detected by this test will likely require a dose increase to achieve effective inhibition of platelet aggregation.
Dosing of drugs that are metabolized through CYP2C19 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 CYP2C19. CYP2C19 poor metabolizers may fail to activate clopidogrel, a prodrug. Consideration of increased dosing or alternative anticoagulant is suggested.
The following is a partial listing of drugs known to affect CYP2C19 activity as of the date of this report.
Drugs that undergo metabolism by CYP2C19:
-Anticoagulants: clopidogrel (Plavix)
-Anticonvulsants: mephenytoin, diazepam, phenytoin, primidone
-Antidepressants: amitriptyline, citalopram, S-citalopram, clomipramine
-Proton pump inhibitors: lansoprazole, omeprazole, pantoprazole
-Miscellaneous drugs: progesterone, propranolol, R-warfarin (less active isomer), proguanil, diazepam
Coadministration may decrease the rate of elimination of other drugs metabolized by CYP2C19
Drugs known to increase CYP2C19 activity:
-Carbamazepine, prednisone, rifampin
Coadministration of these drugs increase synthesis of CYP2C19 and increase the rate of elimination of drugs metabolized by CYP2C19
Drugs known to decrease CYP2C19 activity:
-Chloramphenicol, cimetidine, felbamate, fluoxetine, fluvoxamine, indomethacin, ketoconazole, lansoprazole, modafinil, omeprazole, probenecid, ticlopidine, topiramate
Coadministration will decrease the rate of metabolism of CYP2C19 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.
The normal genotype for CYP2C19 is CYP2C19*1. Other genotypes that lead to inactive or reduced activity alleles include CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*6, CYP2C19*7, and CYP2C19*8. An individual who is homozygous wild type, or CYP2C19*1/CYP2C19*1, is considered an extensive metabolizer. An individual who is heterozygous for the wild type and variant genotype is considered an intermediate metabolizer. An individual who is either a homozygous variant or compound heterozygous variant genotype is considered a poor metabolizer. Individuals who are homozygous for *1 but who also have the CYP2C19*17 promoter polymorphism may have enhanced metabolism of drugs, and may require higher drug doses to maintain therapeutic effectiveness. Individuals with a *17 allele may activate prodrugs, such as clopidogrel, to the active metabolites to a greater extent than extensive metabolizers.
Drug-drug interactions and drug/metabolite inhibition must be considered when dealing with heterozygous individuals. Drug/metabolite inhibition can occur, resulting in inhibition of residual functional CYP2C19 catalytic activity.
Patients may also develop toxicity problems if liver and kidney functions 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 CYP2C19. 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. Blaisdell J, Mohrenweiser H, Jackson J, et al: Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics 2002 Dec;12(9):703-711
2. Jeppesen U, Gram LF, Vistisen K, Loft S, et al: Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. Eur J Clin Pharmacol 1996;51(1):73-78
3. Simon T, Verstuyft C, Mary-Krause M, et al: Genetic determinants response to clopidogrel and cardiovascular events. N Engl J Med 2009;360(4):363-375
4. Mega J, Close S, Wiviott D, et al: Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-362
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. The CYP2C19 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 and intron/exon boundaries of the promoter and exons 1, 3, 4, and 5 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.
Varies; 8 a.m.
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.
81225-CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (eg, drug metabolism), gene analysis, common variants (eg, *2, *3, *4, *8, *17)
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|
|2C19Q||CYP2C19 Sequencing||In Process|
|31969||2C19 Genotype Star Alleles||In Process|
|31987||2C19 -806C>T (*17)||In Process|
|24058||2C19 1A>G (*4)||In Process|
|24059||2C19 358T>C (*8)||In Process|
|24060||2C19 395G>A (*6)||In Process|
|24061||2C19 636G>A (*3)||In Process|
|24062||2C19 681G>A (*2)||In Process|
|24063||2C19 IVS5+2T>A (*7)||In Process|
|24066||2C19 Reviewed by||In Process|