Test Catalog

Test Id : COMTQ

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Catechol-O-Methyltransferase (COMT) Genotype, Varies

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Prediction of response to nicotine replacement therapy for smoking cessation

 

Investigation of inhibitor dosing for decreasing levodopa metabolism

 

Research use for assessing estrogen metabolism

Method Name
A short description of the method used to perform the test

Real-Time Polymerase Chain Reaction (PCR) with Allelic Discrimination Analysis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

COMT Genotype, V

Aliases
Lists additional common names for a test, as an aid in searching

Catechol O-methyltransferase

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

This test should not be ordered for pheochromocytoma or paraganglioma assessment. Instead, order 1 of the following:

-METAF / Metanephrines, Fractionated, 24 Hour, Urine

-PMET / Metanephrines, Fractionated, Free, Plasma

-CATU / Catecholamine Fractionation, Free, 24 Hour, Urine

-CATP / Catecholamine Fractionation, Free, Plasma

 

Testing is available as the single gene assay (this test) and as a part of a psychotropic pharmacogenomics panel. If genotype testing for psychotropic medications is desired, order PSYQP / Psychotropic Pharmacogenomics Gene Panel, Varies.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Genotype Test List in Special Instructions for a list of tests that can be ordered together.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

 

Specimen Type: Extracted DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 50 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Neurology Specialty Testing Client Test Request (T732)

-Therapeutics Test Request (T831)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

Blood: 0.4 mL

Saliva: 1 swab

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Prediction of response to nicotine replacement therapy for smoking cessation

 

Investigation of inhibitor dosing for decreasing levodopa metabolism

 

Research use for assessing estrogen metabolism

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. 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. Variants in the COMT gene are therefore designated in the literature by the position of the amino acid change in both the short and long form of the enzyme. A single nucleotide variant (SNV) in exon 4 of the gene produces an amino acid change from valine to methionine (Val108/158Met). The presence of methionine at this position 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 (valine at this position). This variant has been associated with prediction of response and risk of relapse when using nicotine replacement therapy for smoking cessation.(3)

 

The following information outlines the relationship between the polymorphism detected in this assay and the effect on the activity of the enzyme produced by that allele:

 

Amino acid change

cDNA nucleotide change

(NM_000754.3)

Effect on enzyme activity/metabolism

None (wild-type)

None (wild type)

Normal activity

p.Val158Met

(known as Val108Met)

c.472G>A

Reduced activity

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.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Samples may contain donor DNA if obtained from patients who received non-leukoreduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell transplantation, a pretransplant DNA specimen is recommended for testing.

 

COMT genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's catechol-O-methyltransferase (COMT) status.

 

This test does not detect variants other than those listed. Variants in primer binding may affect test results and ultimately the genotyping calls made.

 

Absence of a detectable variant does not rule out the possibility that a patient has an intermediate or poor metabolizer phenotype. Patients with a normal (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:

-Alpha-methyl DOPA

-Apomorphine

-Benserazide

-Bitolterol

-Dihydroxyphenylserine

-Dobutamine

-Dopamine

-Epinephrine

-2-Hydroxyestrogens

-4-Hydroxyestogens

-Isoetherine

-Isoprenaline

-Isoproterenal

-Norepinephrine

-Rimiterol

Coadministration may decrease the rate of elimination of other drugs metabolized by COMT.

 

Drugs that undergo structural modification but are not metabolized by COMT:

-Albuterol

-Metaproterenol

-Methoxamine

-Phenylephrine

-Perbuterol

-Terbutaline

Coadministration will not decrease the rate of elimination metabolism of other drugs metabolized by COMT.

 

Drugs known to inhibit COMT activity:

-Entacapone

-Tolcapone

-Nitecapone

 

Dietary components that inhibit COMT activity:

-Quercetin

-Tea catechins

Coadministration will decrease the rate of metabolism of COMT metabolized drugs, increasing the possibility of toxicity, including in heterozygous individuals.

Clinical Reference
Recommendations for 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. Annu Rev Pharmacol Toxicol. 1999;39:19-52. doi: 10.1146/annurev.pharmtox.39.1.19

2. Sun H, Guo S, Chen D, et al: Association of functional COMT Val108/Met polymorphism with smoking cessation in a nicotine replacement therapy. J Neural Transm (Vienna). 2012;119(12):1491-1498. doi: 10.1007/s00702-012-0841-8

3. Herman AI, Jatlow PI, Gelernter J, Listman JB, Sofuoglu M: COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers. Pharmacogenomics J. 2013;13(6):490-497. doi: 10.1038/tpj.2013.1

4. Worda C, Sator MO, Schneeberger C, Jantschev T, Ferlitsch K, Huber JC: Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women. Hum Reprod. 2003;18(2):262-266. doi: 10.1093/humrep/deg059

5. Shield AJ, Thomae BA, Eckloff BW, Wieben ED, Weinshilboum RM: Human catechol O-methyltransferase genetic variation: gene resequencing and functional characterization of variant allozymes. Mol Psychiatry. 2004;9(2):151-160. doi: 10.1038/sj.mp.4001386

6. Crews KR, Monte AA, Huddart R, et al: Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther. 2021 Jan 2. doi: 10.1002/cpt.2149. Epub ahead of print

Method Description
Describes how the test is performed and provides a method-specific reference

Genomic DNA is extracted from whole blood or saliva. Genotyping for COMT alleles is performed using a polymerase chain reaction (PCR)-based 5'-nuclease assay. Fluorescently labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the variant. If the detection probe is an exact match to the target DNA, the 5'-nuclease polymerase degrades the probe, the reporter dye is released from the effects of the quencher dye, and a fluorescent signal is detected. Genotypes are assigned based on the allele-specific fluorescent signals that are detected.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 8 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood/Saliva swab: 2 weeks Extracted DNA: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US 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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

0032U

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
COMTQ COMT Genotype, V 74511-7
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
610124 COMT Genotype 74511-7
610125 COMT Phenotype 93411-7
610126 Interpretation 69047-9
610127 Additional Information 48767-8
610128 Method 85069-3
610129 Disclaimer 62364-5
610130 Reviewed by 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports