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Interpretive Handbook

Test 89401 :
Cytochrome P450 1A2 Genotype

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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**


None (wild type)

None (wild type)

Extensive (normal) metabolizer




Decreased activity and decreased inducibility




Increased inducibility




Greatly reduced activity




Decreased activity




No activity




No activity




No activity




No activity




No activity




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.

Useful For Suggests clinical disorders or settings where the test may be helpful

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

Interpretation Provides information to assist in interpretation of the test results

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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

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