Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

COMT
83301
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:
An interpretive report will be provided.
Clinical References: 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
Catechol-O-Methyltransferase Genotype
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
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