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HelpTest ID: COMTQ Catechol-O-Methyltransferase (COMT) Genotype, 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
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
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)
Useful For
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
Real-Time Polymerase Chain Reaction (PCR) with Allelic Discrimination Analysis
Reporting Name
COMT Genotype, VSpecimen Type
VariesSpecimen Minimum Volume
Blood: 0.4 mL
Saliva: 1 swab
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
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. 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
An interpretive report will be provided.
Interpretation
An interpretive report will be provided.
Clinical Reference
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
Day(s) Performed
Monday through Friday
Report Available
3 to 8 daysTest Classification
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
0032U
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| COMTQ | COMT Genotype, V | 74511-7 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 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 |
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