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Test ID: 2C19R Cytochrome P450 2C19 Genotype, Varies


Ordering Guidance


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 desired, order PGXQP / Focused Pharmacogenomics Panel, Varies.

 

If genotype testing for psychotropic medications is desired, order PSYQP / Psychotropic Pharmacogenomics Gene Panel, Varies.



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 patients who may be at risk for altered metabolism of drugs that are modified by cytochrome P450 2C19

 

Predicting anticoagulation response to clopidogrel

Method Name

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

Reporting Name

CYP2C19 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 including the intestines and liver. One of these CYP450 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 (also referred to 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:

 CYP2C19a 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.

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 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.

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. 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. 2020 Aug;10.1002/cpt.2015. 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. 2018 Feb;103(2):349

6. Moriyama B, Obeng AO, Barbarino J, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy. Clin Pharmacol Ther. 2017;102(1):45-51. doi: 10.1002/cpt.583

7. 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;98(2):127-134. doi: 10.1002/cpt.147

8. Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) 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

9. Blaisdell J, Mohrenweiser H, Jackson J, et al: Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics. 2002;12(9):703-711. doi: 10.1097/00008571-200212000-00004

10. Mega JL, Close SL, Wiviott SD, et al: Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354-362. doi: 10.1056/NEJMoa0809171

Day(s) Performed

Monday through Friday

Report Available

1 to 5 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

81225

LOINC Code Information

Test ID Test Order Name Order LOINC Value
2C19R CYP2C19 Genotype, V 57132-3

 

Result ID Test Result Name Result LOINC Value
610089 CYP2C19 Genotype 57132-3
610090 CYP2C19 Phenotype 79714-2
610567 CYP2C19 Activity Score In Process
610091 Interpretation 69047-9
610092 Additional Information 48767-8
610093 Method 85069-3
610094 Disclaimer 62364-5
610095 Reviewed by 18771-6
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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