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Test ID 1A2 Cytochrome P450 1A2 Genotype

Useful For

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

Method Name

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

Reporting Name

CYP1A2 Genotype

Specimen Type

Whole Blood EDTA

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.

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

0.3 mL

Specimen Stability Information

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

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.

Reference Values

An interpretive report will be provided.

Cautions

Rare variants may be present and could lead to false-negative or false-positive results. If results obtained do not match the clinical findings (phenotype), additional testing should be considered.

 

Blood samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow 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 blood or marrow transplantation, a pre-transplant DNA specimen is recommended for testing.

 

CYP1A2 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's CYP1A2 status.

 

This method may not detect all variants that result in altered CYP1A2 activity. Therefore, absence of a detectable gene variant does not rule out the possibility that a patient has an altered CYP1A2 metabolism due to other CYP1A2 variants that cannot be detected with this method. Furthermore, when 2 or more gene variants are identified, the cis-/trans- status (whether the variants are on the same or opposite chromosomes) is not always known.  

 

The frequency of variants which cause altered CYP1A2 metabolism has not been fully characterized in all ethnic groups. Patients with an ultrarapid, extensive (normal), or intermediate genotype may have CYP1A2 enzyme activity inhibited or induced by a variety of substances, medications, or their metabolites.

Day(s) Performed

Tuesday, 8 a.m.

Report Available

2 days (Not reported Saturday or Sunday)

Performing Laboratory

Mayo Medical Laboratories in Rochester

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

NY State Approved

Conditional