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

CATU
9276
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:
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
Catecholamine Fractionation, Free, Urine
Clinical Information: The catecholamines (dopamine, epinephrine, and norepinephrine) are derived
from tyrosine via a series of enzymatic conversions. All 3 catecholamines are important neurotransmitters
in the central nervous system and play crucial roles in the autonomic regulation of many homeostatic
functions, namely, vascular tone, intestinal and bronchial smooth muscle tone, cardiac rate and
contractility, and glucose metabolism. Their actions are mediated via alpha and beta adrenergic receptors
and dopamine receptors, all existing in several subforms. The 3 catecholamines overlap but also differ in
their receptor activation profile and consequent biological actions. The systemically circulating fraction of
Current as of January 3, 2013 2:22 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 392