Sorted By Test Name - Mayo Medical Laboratories

COMTO
60336
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
4 17.5-49.9 Strongly positive
5 50.0-99.9 Strongly positive
6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Allergic diseases. In Clinical Diagnosis and Management by
Laboratory Methods. 21st edition. Edited by McPherson RA, Pincus MR. WB Saunders, Publ, New York,
Chapter 53, Part VI, pp. 961-971, 2007
Catechol-O-Methyltransferase (COMT) Genotype, Saliva
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. Functional polymorphisms have been identified in the gene encoding COMT that lead to highand
low-activity forms of the enzyme.(4) These functional polymorphisms are designated 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 *1. A second functional polymorphism has been identified in
exon 4 that results in a threonine substitution for alanine (Ala52/102Thr). This polymorphism, COMT*3,
reduces the maximum activity of the variant enzyme by 40% compared to the wild-type enzyme. 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)
Useful For: Early identification of patients who may show cognitive improvement with treatment for
schizophrenia; this is associated with the *2/*2 genotype Investigation of inhibitor dosing for decreasing
L-dopa metabolism Research use for assessing estrogen metabolism
Interpretation: An interpretive report will be provided. The normal genotype (wild type) for COMT is
*1/*1. Other genotypes that lead to reduced activity alleles include COMT*2 (Val108/158Met) and
COMT*3 (Ala52/102Thr). 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: COMT Allele
Amino Acid Change Effect on Enzyme Activity/Metabolism *1 None (wild-type) Normal/Extensive *2
Val108/158Met Reduced/Poor *3 Ala52/102Thr Reduced/Intermediate
Reference Values:
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