NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) with Allele-Specific Primer Extension (ASPE)
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Catechol Methyltransferase Genotype
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple whole blood EDTA genotype tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send specimen in original tube.
1. Bone marrow and liver transplants will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions.
2. Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
Forms: 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 (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Ambient (preferred)|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
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:
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Amino Acid Change
Effect on Enzyme Activity/Metabolism
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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 paragangliomas assessment. METAF / Metanephrines, Fractionated, 24 Hour, Urine; PMET / Metanephrines, Fractionated, Free, Plasma; CATU / Catecholamine Fractionation, Free, Urine; or CATP / Catecholamine Fractionation, Plasma, Free should be ordered instead.
Absence of a detectable gene mutation or polymorphism does not rule out the possibility that a patient has an intermediate or poor metabolizer phenotype. Patients with an extensive or intermediate metabolizer genotype may have COMT enzyme activity inhibited by a variety of medications, or their metabolites. The following is a partial listing of drugs known to affect COMT activity.
Drugs that undergo metabolism by COMT:
Coadministration may decrease the rate of elimination of other drugs metabolized by COMT.
Drugs that undergo structural modification but are not metabolized by COMT:
Coadministration will not decrease the rate of elimination metabolism of other drugs metabolized by COMT.
Drugs known to inhibit COMT activity:
Dietary Components that inhibit COMT activity:
Coadministration will decrease the rate of metabolism of COMT metabolized drugs, increasing the possibility of toxicity, including in heterozygous individuals.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. Direct polymorphism analysis for COMT is performed after PCR and allele specific primer extension (ASPE) with Luminex Molecular Diagnostics’ proprietary Universal Tag sorting system on the Luminex 100 xMAP platform. A genotype is assigned based on the allele-specific fluorescent signals that are detected.(Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Wednesday; 8 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Whole Blood: 2 weeks Extracted DNA: 2 months
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479-Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|83301||Catechol Methyltransferase Genotype||In Process|