Sorted By Test Name - Mayo Medical Laboratories

1A2O
60346
Cytochrome P450 1A2 Genotype, Saliva
Clinical Information: Primary metabolism of many drugs is performed by cytochrome P450 (CYP),
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 (see below). The current clinical
application of this test is focused on the impact of allelic variation on antidepressant and antipsychotic
metabolism. CYP1A2-mediated drug metabolism is highly variable. CYP1A2*1A is the wild type or
normal allele. Some individuals have altered CYP1A2 gene sequences that result in synthesis defective
enzyme. These individuals metabolize CYP1A2 substrates poorly. Changes in the promoter impacting
gene induction of the CYP1A2 gene has been observed, which results in either an increase or decrease of
overall metabolic activity. Dosing of drugs that are metabolized through CYP1A2 may require adjustment
based on the individual patient's genotype. Patients who are poor metabolizers may require lower than
usual doses to achieve optimal response. Patients who are ultrarapid metabolizers may benefit from
increased doses. Patients with either ultrarapid or poor metabolism also may benefit by conversion to
other comparable drugs that are not primarily metabolized by CYP1A2. A number of specific
polymorphisms have been found in the CYP1A2 gene that results in enzymatic deficiencies. The
frequency of these polymorphisms varies within the major ethnic groups. All of the identified
polymorphisms associated with CYP1A2 are autosomal recessive. Consequently, only individuals who
are homozygous or compound heterozygous for these polymorphisms are poor metabolizers. Individuals
who are heterozygous, with 1 normal gene and 1 defective polymorphic gene, will have metabolism
intermediate between the extensive (normal) and poor metabolizers. The following information outlines
the relationship between the polymorphisms detected in this assay and the effect on the activity of the
enzyme produced by that allele: Nucleotide Change Effect on Enzyme Metabolism* -3860G->A Lower
inducibility in Asians but increased inducibility in Northern Europeans -2467T->del T Increased
inducibility -729C->T Decreased activity and decreased inducibility -163C->A Increased inducibility
125C->G Greatly reduced activity 558C->A Greatly reduced activity 2116G->A Decreased activity
2385G->A Decreased activity 2473G->A Greatly reduced activity 2499A->T Decreased activity
3497G->A Decreased activity 3533G->A No activity 5090C->T Greatly reduced activity 5166G->A
Decreased activity *Effect of a specific polymorphism 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 with 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
dosing decrease greater than predicted based upon genotype alone. Another complicating factor is that the
CYP1A2 gene 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: Identifying patients who are poor, intermediate, extensive, or ultrarapid metabolizers of
drugs metabolized by CYP1A2 Adjusting dosages for drugs that are metabolized by CYP1A2
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
ultra-rapid metabolizer phenotype. The report will list drugs known to affect metabolism by CYP1A2.
Direct polymorphism analysis for -3860G->A, -2467T->del T, -729C->T, -163C->A, 125C->G,
558C->A, 2116G->A, 2385G->A, 2473G->A, 2499A->T, 3497G->A, 3533G->A, 5090C->T, or
5166G->A is performed following PCR amplification. Direct DNA testing will not detect all the known
mutations that result in decreased or inactive CYP1A2 alleles. This assay does not test for some known
polymorphisms because those polymorphisms have not been associated with alterations in enzymatic
activity. Rare or undescribed variants may not have been found during validation but will be sequence
verified upon detection. See http:///www.cypalleles.ki.se/cyp1a2.html for a full description of CYP1A2
alleles. Absence of a detectable gene mutation or polymorphism does not rule out the possibility that a
patient has a metabolizer status other than predicted above. The frequency of polymorphisms causing poor
metabolism has not been fully characterized in various ethnic groups. Patients with an ultrarapid,
extensive, or intermediate genotype may have CYP1A2 enzyme activity inhibited or induced by a variety
of substances, medications, or their metabolites. The following is a listing of substances known to affect
CYP1A2 activity as the date of this report. Drugs and substances known to increase (induce) CYP1A2
Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 573