Sorted By Test Name - Mayo Medical Laboratories

COMT
83301
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 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 high- and 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-fold 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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