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Test ID: 1A2 Cytochrome P450 1A2 Genotype

Reporting Name

CYP1A2 Genotype

Useful For

Identifying individuals who are poor, intermediate, extensive, or ultrarapid metabolizers of drugs metabolized by CYP1A2 to assist drug therapy decision making

Specimen Type

Whole Blood EDTA


Specimen Required


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.


Specimen Minimum Volume

0.3 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood EDTA Ambient (preferred)
  Refrigerated 

Reference Values

An interpretive report will be provided.

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 U.S. Food and Drug Administration.

CPT Code Information

81479-Unlisted molecular pathology procedure

LOINC Code Information

Test ID Test Order Name Order LOINC Value
1A2 CYP1A2 Genotype 80687-7

 

Result ID Test Result Name Result LOINC Value
45499 1A2 Phenotype Interpretation 69047-9
45501 1A2 -3860g>a 75719-5
45502 1A2 -2467tdel 75714-6
45504 1A2 -729c>t 75725-2
45505 1A2 -163c>a 75722-9
45506 1A2 125c>g 75713-8
45507 1A2 558c>a 75724-5
45508 1A2 2385g>a 75723-7
45509 1A2 2473g>a 75715-3
45510 1A2 2499a>t 75716-1
45511 1A2 3497g>a 75717-9
45512 1A2 3533g>a 75718-7
45513 1A2 5090c>t 75720-3
45514 1A2 5166g>a 75721-1
45517 1A2 Reviewed by 69047-9

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 result in increased, diminished, or abolished catalytic activity and substrate metabolism.

 

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 ultrarapid 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


Effect on Enzyme Metabolism**

*1

None (wild type)

None (wild type)

Extensive (normal) metabolizer

*1K

-729C->T

c.-10+113C->T

Decreased activity and decreased inducibility

*1F

-163C->A

c.-9-154C->A

Increased inducibility

*4

2499A->T

c.1156A->T

Greatly reduced activity

*5

3497G->A

c.1217G->A

Decreased activity

*6

5090C->T

c.1291C->T

No activity

*7

3533G->A

c.1253+1G->A

No activity

*8

5166G->A

c.1367G->A

No activity

*11

558C->A

c.558C->A

No activity

*15

125C->G

c.125C->G

No activity

*16

2473G->A

c.1130G->A

No activity

**The frequency of these variants varies by ethnicity.

*Effect of a specific allele on the activity of the CYP1A2 enzyme can only be estimated since the literature does not provide precise data.  

 

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.

Interpretation

An interpretive report will be provided that includes assay information, genotype, and an interpretation indicating whether results are consistent with a poor, intermediate, extensive, or ultrarapid metabolizer phenotype.

 

The genotype, with associated star alleles, is assigned using standard allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele Nomenclature Database Committee.(1)

 

CYP1A2 activity is also dependent upon hepatic function status, as well as age. Renal function may be important for drugs that are also 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. Human Cytochrome P450 (CYP) Allele Nomenclature Database. Accessed 9/21/15. Available at: http://www.cypalleles.ki.se/cyp1a2.htm

2. Ito M, Katono Y, Oda A, et al: Functional characterization of 20 allelic variants of CYP1A2. Drug Metab Pharmacokinet 2015 Jun;30(3):247-252

3. Zhou H, Josephy PD, Kim D, Guengerick FP: Functional characterization of four allelic variants of human cytochrome P450 1A2. Arch Biochem Biophys 2004 Feb;422(1):23-30

4. 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 Jan;308(1):300-306

5. Saito Y, Hanioka N, Maekawa K, et al: Functional analysis of three CYP1A2 variants found in a Japanese population. Drug Metab Dispos 2005 Dec;33(12):1905-1910

Analytic Time

2 days (Not reported Saturday or Sunday)

Method Name

Polymerase Chain Reaction (PCR) with Allele-Specific Primer Extension (ASPE)/Bead Hybridization with Fluorescence Detection

Forms

1. 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 (576) is available in Special Instructions.

2. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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