Identifying patients who may be at risk for altered metabolism of drugs that are modified by cytochrome P450 2C19
Predicting anticoagulation response to clopidogrel
Real-Time Polymerase Chain Reaction (PCR) with Allelic Discrimination Analysis
Clopidogrel (Plavix)
CYP2C19
Cytochrome P450 2C19 Genotyping
Plavix
Proton pump inhibitor
PPI
Voriconazole
escitalopram
citalopram
Varies
Testing is available as the single gene assay (this test) and as a part of a psychotropic or focused pharmacogenomics panel.
If multiple pharmacogenomic genotype testing is needed, consider PGXQP / Focused Pharmacogenomics Panel, Varies.
If genotype testing for psychotropic medications is requested, order PSYQP / Psychotropic Pharmacogenomics Gene Panel, Varies.
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
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)
-Cardiovascular Test Request (T724)
Blood: 0.4 mL
Saliva, extracted DNA: see Specimen Required
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Identifying patients who may be at risk for altered metabolism of drugs that are modified by cytochrome P450 2C19
Predicting anticoagulation response to clopidogrel
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 including the intestines and liver. One of these CYP enzymes, CYP2C19, participates in the metabolism of a wide variety of drugs, including the activation of the anticoagulant clopidogrel and the inactivation of citalopram.
CYP2C19 drug metabolism is variable among individuals. Some individuals have CYP2C19 genetic variants that lead to severely diminished or absent CYP2C19 catalytic activity (ie, poor metabolizers). The frequency of CYP2C19 variants (formerly known as polymorphisms) depends on ethnicity. CYP2C19 variants that produce poor metabolizers are found with frequencies of 2% to 5% in the White population, 4% in African Americans, 13% to 23% in Asians, and 38% to 79% in Polynesians and Micronesians.
The following table displays the CYP2C19 variants detected by this assay, the corresponding star allele, and the effect on CYP2C19 enzyme activity.
Table. Enzyme Activity of Individual Star Alleles
| CYP2C19 allele | cDNA nucleotide change (NM_000769.1) | Effect on enzyme activity |
| *1 | None (wild type) | Normal (extensive) activity |
| *2 | c.681G>A | No activity |
| *3 | c.636G>A | No activity |
| *4 | c.1A>G | No activity |
| *5 | c.1297C>T | No activity |
| *6 | c.395G>A | No activity |
| *7 | c.819+2T>A | No activity |
| *8 | c.358T>C | No activity |
| *9 | c.431G>A | Decreased activity |
| *10 | c.680C>T | Decreased activity |
| *17 | c.-806C>T | Enhanced activity |
| *35 | c.332-23A>G in the absence of c.681G>A | No activity |
CYP2C19 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(3-8), and an exhaustive review of the CYP2C19 literature(9-10). Individuals without a detectable CYP2C19 variant will have the predicted phenotype of an extensive drug metabolizer and are designated as CYP2C19*1/*1. If an individual is homozygous or compound heterozygous for alleles 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. Individuals with the CYP2C19*17 allele (in the absence of any inactive or decreased activity alleles) may have enhanced metabolism of drugs. 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 CYP2C19. It is important to interpret the results of testing in the context of other coadministered drugs.
An interpretive report will be provided.
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 when treating intermediate metabolizers. It is important to interpret the results of testing and dose adjustments in the context of hepatic and renal function and patient age.
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.
CYP2C19 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's CYP2C19 status.
This method may not detect all variants that result in altered CYP2C19 activity. Therefore, absence of a detectable variant does not rule out the possibility that a patient has altered CYP2C19 metabolism due to other CYP2C19 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.
This test is designed to detect only the variants specified above. Other variants in the primer binding regions can affect testing and, ultimately, the genotype and phenotype predictions made.
1. PharmVar: Pharmacogene Variation Consortium. Updated September 26, 2022. Accessed October 6, 2022. Available at www.pharmvar.org/
2. Clinical Pharmacogenetics Implementation Consortium (CPIC). Updated September 23, 2022. Accessed October 14, 2020. Available at https://cpicpgx.org/
3. Scott SA, Sangkuhl K, Stein CM, et al: Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013 Sep;94(3):317-323. doi: 10.1038/clpt.2013.105
4. Lima JJ, Thomas CD, Barbarino J, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C19 and proton pump inhibitor dosing. Clin Pharmacol Ther. 2021 Jun;109(6):1417-1423. doi: 10.1002/cpt.2015
5. Moriyama B, Obeng AO, Barbarino J, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2C19 and voriconazole therapy. Clin Pharmacol Ther. 2017 Jul;102(1):45-51. doi: 10.1002/cpt.583. Erratum in: Clin Pharmacol Ther. 2018 Feb;103(2):349
6. Hicks JK, Bishop JR, Sangkuhl K, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015 Aug;98(2):127-134. doi: 10.1002/cpt.147
7. Hicks JK, Sangkuhl K, Swen JJ, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017;102(1):37-44. doi: 10.1002/cpt.597
8. 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. doi: 10.1097/00008571-200212000-00004
9. Mega JL, Close SL, Wiviott SD, et al: Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 Jan;360(4):354-362. doi: 10.1056/NEJMoa0809171
Genomic DNA is extracted from whole blood or saliva. Genotyping for CYP2C19 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.(Unpublished Mayo method)
Monday through Friday
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
81225
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| 2C19R | CYP2C19 Genotype, V | 57132-3 |
| 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.
|
|---|---|---|
| 610089 | CYP2C19 Genotype | 57132-3 |
| 610090 | CYP2C19 Phenotype | 79714-2 |
| 610567 | CYP2C19 Activity Score | 104667-1 |
| 610091 | Interpretation | 69047-9 |
| 610092 | Additional Information | 48767-8 |
| 610093 | Method | 85069-3 |
| 610094 | Disclaimer | 62364-5 |
| 610095 | Reviewed by | 18771-6 |