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Test ID COMTO Catechol-O-Methyltransferase (COMT) Genotype, Saliva

Useful For

Early identification of patients who may show cognitive improvement with treatment for schizophrenia; this is associated with the COMT*2/ COMT*2 genotype

 

Investigation of inhibitor dosing for decreasing L-dopa metabolism

 

Research use for assessing estrogen metabolism

 

Genotyping patients who prefer not to have venipuncture done

Method Name

Polymerase Chain Reaction (PCR) with Allele-Specific Primer Extension (ASPE)

Reporting Name

COMT Genotype, Saliva

Specimen Type

Saliva

Multiple saliva genotype tests can be performed on a single specimen after a single extraction. See Multiple Saliva Genotype Tests in Special Instructions for a list of tests that can be ordered together.

 

Container/Tube: Oragene DNA Self-Collection Kit (Supply T651: fees apply)

Specimen Volume: Full tube

Collection Instructions:

1. Fill to tube line.           

2. Send specimen in original container per kit instructions.

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

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Saliva Ambient

Clinical Information

Catechol-O-methyltransferase (COMT) is involved in phase II (conjugative) metabolism of catecholamines and catechol drugs, such as dopamine, as well as the catechol-estrogens. COMT transfers a donor methyl-group from S-adenosylmethionine to acceptor hydroxy groups on catechol structures (aromatic ring structures with vicinal hydroxy-groups).(1) Bioactive catecholamine metabolites are metabolized by COMT in conjunction with monoamine oxidase (MAO):

-Norepinephrine is methylated by COMT-forming normetanephrine.

-Epinephrine is methylated by COMT-forming metanephrine.

-Dopamine is converted to homovanillic acid through the combined action of MAO and COMT.

 

Parkinsonism patients receiving levodopa (L-dopa) therapy are frequently also prescribed a COMT inhibitor to minimize metabolism of L-dopa by COMT, thereby prolonging L-dopa action.

 

COMT is also involved in the inactivation of estrogens. Estradiol can be hydroxylated forming the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol.(2) These hydroxylated estradiols are methylated by COMT, forming the corresponding methoxyestradiols. Several studies have indicated the increased risk of breast cancer due to low-activity COMT.(3)

 

The gene encoding COMT is transcribed from alternative promoters to produce 2 forms of the enzyme, a soluble short form of the enzyme and a membrane-bound long form. Variants in the COMT gene are therefore designated in the literature by the position of the amino acid change in both the short and long form of the enzyme. A single nucleotide polymorphism in exon 4 of the gene produces an amino acid change from valine to methionine (Val108/158Met). This polymorphism, COMT*2, reduces the maximum activity of the variant enzyme by 25% and also results in significantly less immunoreactive COMT protein, resulting in a 3- to 4-fold decrease in activity compared to wild type COMT*1. The COMT*2 polymorphism has been linked to prefrontal cortex cognitive response to antipsychotic medications. Schizophrenia patients homozygous for the *2 polymorphism displayed improved cognition following drug treatment. Patients homozygous for *1 did not have improved cognition following treatment.(6) A second polymorphism has been identified in exon 4 that results in a threonine substitution for alanine (Ala52/102Thr). This polymorphism, COMT*3, does not reduce enzyme activity and is predicted to be a normally functioning allele.

Reference Values

An interpretive report will be provided.

Cautions

Saliva 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 pretransplant DNA specimen is recommended for testing.

 

Catechol-O-methyltransferase (COMT) genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's COMT status.

 

This test does not detect polymorphisms other than those listed. Mutations in primer binding may affect test results and ultimately the genotyping calls made.

 

This test should not be ordered for pheochromocytoma or paraganglioma assessment. Instead, order 1 of the following:

-METAF / Metanephrines, Fractionated, 24 Hour, Urine

-PMET / Metanephrines, Fractionated, Free, Plasma

-CATU / Catecholamine Fractionation, Free, 24 Hour, Urine

-CATP / Catecholamine Fractionation, Plasma, Free

 

Absence of a detectable gene mutation or polymorphism does not rule out the possibility that a patient has an intermediate or poor metabolizer phenotype. Patients with an extensive or intermediate metabolizer genotype may have COMT enzyme activity inhibited by a variety of medications or their metabolites. The following is a partial listing of drugs known to affect COMT activity.

 

Drugs that undergo metabolism by COMT:

-Alpha-methyl dopa

-Apomorphine

-Benserazide

-Bitolterol

-Dihydroxyphenylserine

-Dobutamine

-Dopamine

-Epinephrine

-2-Hydroxyestrogens

-4-Hydroxyestogens

-Isoetherine

-Isoprenaline

-Isoproterenal

-Norepinephrine

-Rimiterol

Coadministration may decrease the rate of elimination of other drugs metabolized by COMT.

 

Drugs that undergo structural modification but are not metabolized by COMT:

-Albuterol

-Metaproterenol

-Methoxamine

-Phenylephrine

-Perbuterol

-Terbutaline

Coadministration will not decrease the rate of elimination/metabolism of other drugs metabolized by COMT.

 

Drugs known to inhibit COMT activity:

-Entacapone

-Tolcapone

-Nitecapone

 

Dietary components that inhibit COMT activity:

-Quercetin

-Tea catechins

Coadministration will decrease the rate of metabolism of COMT-metabolized drugs, increasing the possibility of toxicity, particularly in heterozygous individuals.

Day(s) Performed

Wednesday; 8 a.m.

Report Available

2 days (Not reported on 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