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HelpTest ID: 1A2Q Cytochrome P450 1A2 Genotype, Varies
Ordering Guidance
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.
Order PGXQP / Focused Pharmacogenomics Panel, Varies if multiple pharmacogenomic genotype testing is desired.
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 individuals who are poor, intermediate, normal (extensive) or rapid metabolizers of drugs metabolized by cytochrome P450 1A2 to assist drug therapy decision making
Method Name
Real-Time Polymerase Chain Reaction (PCR) with Allelic Discrimination Analysis
Reporting Name
CYP1A2 Genotype, VSpecimen Type
VariesSpecimen Minimum Volume
Blood: 0.4 mL
Saliva: 1 swab
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
The cytochrome P450 (CYP) family is involved in the primary metabolism of many drugs. The CYPs are a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues including the intestines and liver. One of these CYP enzymes, CYP1A2, is wholly or partially responsible for the hydroxylation or dealkylation of many commonly prescribed drugs.
CYP1A2-mediated drug metabolism is highly variable. A number of variants have been identified in the CYP1A2 gene that results in increased, diminished, or abolished catalytic activity and substrate metabolism. The frequency of these variants varies by ethnicity.
Dosing of drugs that are metabolized through CYP1A2 may require adjustment based on the CYP1A2 genotype. Individuals who are poor metabolizers may require lower than usual doses to achieve optimal response, whereas individuals who are ultrarapid metabolizers may benefit from increased doses. CYP1A2 phenotype is predicted based upon the number of functional, partially functional, nonfunctional, and inducible alleles present in a sample. In the absence of clear guidance on dosing for various metabolizer phenotypes, patients with either rapid or poor metabolism also may benefit by switching to another comparable drug that is not primarily metabolized by CYP1A2 or by therapeutic drug monitoring where applicable.
The following table outlines the relationship between the variations (star alleles) detected in this assay and the effect on the activity of the enzyme produced by that allele.
|
CYP1A2 allele |
Nucleotide change (legacy nomenclature) |
cDNA nucleotide change (NM_000761.4) |
|
|
*1 |
None (wild type) |
None (wild type) |
Normal (extensive) activity |
|
*1F |
-163C>A |
c.-9-154C>A |
Increased inducibility |
|
*1K |
-729C>T |
c.-10+113C>T |
Decreased activity and decreased inducibility |
|
*6 |
5090C>T |
c.1291C>T |
No activity |
|
*7 |
3533G>A |
c.1253+1G>A |
No activity |
a. Effect of a specific allele on the activity of the CYP1A2 enzyme can only be estimated since the literature does not provide precise data.(1-5)
A complicating factor in correlating CYP1A2 genotype to CYP1A2 phenotype is that some drugs or their metabolites are inhibitors of CYP1A2 catalytic activity. These drugs may reduce CYP1A2 catalytic activity. Consequently, an individual may require a dose decrease greater than predicted based upon genotype alone. Another complicating factor is that CYP1A2 is inducible by several drugs and environmental agents (eg, cigarette smoke) and the degree of inducibility is under genetic control. It is important to interpret the results of testing in the context of other coadministered drugs and environmental factors.
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.(6)
CYP1A2 activity is also dependent upon hepatic function status, as well as age. Renal function may be important for drugs that are excreted in urine. Patients may develop drug toxicity if hepatic or renal function is decreased. Drug metabolism is known to decrease with age. It is important to interpret the results of testing and dose adjustments in the context of hepatic and renal function and age.
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.
Clinical Reference
1. Ito M, Katono Y, Oda A, Hirasawa N, Hiratsuka M: Functional characterization of 20 allelic variants of CYP1A2. Drug Metab Pharmacokinet. 2015 Jun;30(3):247-252. doi: 10.1016/j.dmpk.2015.03.001
2. Zhou H, Josephy PD, Kim D, Guengerich FP: Functional characterization of four allelic variants of human cytochrome P450 1A2. Arch Biochem Biophys. 2004 Feb;422(1):23-30. doi: 10.1016/j.abb.2003.11.019
3. Murayama N, Soyama A, Saito Y, et al: Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes. J Pharmacol Exp Ther. 2004 Mar;308(3):1219
4. Murayama N, Soyama A, Saito Y, et al: J Pharmacol Exp Ther. 2004;308(1):300-306. doi: 10.1124/jpet.103.055798
5. Saito Y, Hanioka N, Maekawa K, et al. Functional analysis of three CYP1A2 variants found in a Japanese population. Drug Metab Dispos. 2005;33(12):1905-1910. doi: 10.1124/dmd.105.005819
6. PharmVar. Pharmacogene Variation Consortium. Updated March 3, 2021. Accessed March 22, 2021. Available at www.pharmvar.org/
Day(s) Performed
Monday through Friday
Report Available
3 to 8 daysTest Classification
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.CPT Code Information
0031U
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| 1A2Q | CYP1A2 Genotype, V | 80687-7 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 610075 | CYP1A2 Genotype | 72884-0 |
| 610076 | CYP1A2 Phenotype | 94254-0 |
| 610077 | Interpretation | 69047-9 |
| 610078 | Additional Information | 48767-8 |
| 610079 | Method | 85069-3 |
| 610080 | Disclaimer | 62364-5 |
| 610081 | Reviewed by | 18771-6 |
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