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

Reporting Name

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

Specimen Type


Advisory Information

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

Specimen Required

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.


Supplies: DNA Saliva Collection Kit (T651)

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

Specimen Volume: Full tube

Collection Instructions:

1. Fill to tube line.

2. Send specimen in original container per kit instructions.

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Saliva Ambient

Reference Values

An interpretive report will be provided.

Day(s) and Time(s) Performed

Wednesday; 8 a.m.

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
COMTO COMT Genotype, Saliva In Process


Result ID Test Result Name Result LOINC Value
32925 Reviewed by No LOINC Needed
32926 Catechol Methyltransferase Genotype In Process

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.(4) 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.


An interpretive report will be provided.


The normal genotype (wild type) for COMT is *1/*1. COMT*2 (Val108/158Met) leads to a reduced activity allele. COMT*3 (Ala52/102Thr) is a normal activity allele.


The following information outlines the relationship between polymorphisms detected in this assay and the effect on the activity of the enzyme produced by that allele:



Amino Acid Change

Effect on Enzyme


None (wild-type)








Clinical Reference

1. Weinshilboum RM, Otterness DM, Szumlanski CL: Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Ann Rev Pharmacol Toxicol 1999;39:19-52

2. Zhu BT, Conney, AH: Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis 1998;19:1-27

3. Worda C, Sator MO, Schneeberger C, et al: Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women. Hum Reproduct 2003 Feb;18(2):262-266

4. Shield AJ, Thomae BA, Eckloff BW, et al: Human catechol-O-methyltransferase genetic variation: gene resequencing and functional characterization of variant allozymes. Mol Psychiatry 2004 February;9(2):151-160

5. van Duursen MBM, Sanderson JT, de Jong PC, et al: Phytochemicals inhibit catechol-O-methyltransferase activity in cytosolic fractions from healthy human mammary tissues; Implications for catechol estrogen-induced DNA damage. Toxicol Sci 2004;81:316-324

6. Weickert TW, Goldberg TE, Mishara A, et al: Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications. Psychiatry 2004 Nov 1;56(9):677-682 

Analytic Time

2 days (Not reported on Saturday or Sunday)

Method Name

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


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 (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information: