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Genetics Home Reference: your guide to understanding genetic conditions
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COMT

Reviewed September 2007

What is the official name of the COMT gene?

The official name of this gene is “catechol-O-methyltransferase.”

COMT is the gene's official symbol. The COMT gene is also known by other names, listed below.

What is the normal function of the COMT gene?

The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase. Two versions of this enzyme are made from the gene. The longer form, called membrane-bound catechol-O-methyltransferase (MB-COMT), is chiefly produced by nerve cells in the brain. Other tissues, including the liver, kidneys, and blood, produce a shorter form of the enzyme called soluble catechol-O-methyltransferase (S-COMT). This form of the enzyme helps control the levels of certain hormones.

In the brain, catechol-O-methyltransferase helps break down certain chemical messengers called neurotransmitters. These chemicals conduct signals from one nerve cell to another. Catechol-O-methyltransferase is particularly important in an area at the front of the brain called the prefrontal cortex, which organizes and coordinates information from other parts of the brain. This region is involved with personality, planning, inhibition of behaviors, abstract thinking, emotion, and working (short-term) memory. To function efficiently, the prefrontal cortex requires signalling by neurotransmitters such as dopamine and norepinephrine. Catechol-O-methyltransferase helps maintain appropriate levels of these neurotransmitters in this part of the brain.

How are changes in the COMT gene related to health conditions?

22q11.2 deletion syndrome - associated with the COMT gene

The characteristic signs and symptoms of 22q11.2 deletion syndrome result from a deletion of a small piece of chromosome 22. The chromosomal region that is typically deleted contains 30 to 40 genes, including the COMT gene. As a result of the deletion, people with this disorder have only one copy of the COMT gene in each cell instead of the usual two copies.

A loss of one copy of the COMT gene in each cell leads to abnormal regulation of catechol-O-methyltransferase levels in the brain. Researchers believe that changes involving this enzyme in the prefrontal cortex may help explain the increased risk of behavioral problems and mental illness associated with 22q11.2 deletion syndrome. Little is known, however, about the relationship between catechol-O-methyltransferase activity and the specific mental and emotional problems characteristic of this condition. People with 22q11.2 deletion syndrome are much more likely than people without the condition to develop schizophrenia, depression, anxiety, and bipolar disorder.

other disorders - associated with the COMT gene

Variations in the COMT gene also may be associated with mental illness in people without 22q11.2 deletion syndrome. Researchers have looked extensively at the potential connection between changes in the COMT gene and the risk of developing schizophrenia. Most studies have focused on the effects of a particular common variation (polymorphism) in catechol-O-methyltransferase. This variation alters a single protein building block (amino acid) in the enzyme, replacing the amino acid valine with the amino acid methionine. In the longer form of the enzyme, this variation occurs at position 158 (written as Val158Met). In the shorter form of the enzyme, it occurs at position 108 (written as Val108Met). Researchers often shorten this notation to Val108/158Met. The change affects the stability and activity of catechol-O-methyltransferase, which alters the enzyme's ability to break down neurotransmitters in the prefrontal cortex.

Studies of the Val108/158Met polymorphism in people with schizophrenia have had mixed results. While most studies report no evidence of heightened risk with either methionine or valine at this position, some studies have found a slightly increased risk of schizophrenia in people with valine at position 108/158. Having valine at this position is associated with differences in thought processes that are common in people with schizophrenia, including problems with working memory, inhibition of behavior, and attention. Other changes in the COMT gene may also contribute to these differences. Variations in the COMT gene are among many factors under study to help explain the causes of schizophrenia. A large number of genetic and lifestyle factors, most of which remain unknown, likely determine the risk of developing this condition.

The Val108/158Met polymorphism has also been associated with other disorders that affect thought (cognition) and emotion. For example, researchers have studied this variation as a possible risk factor for bipolar disorder, panic disorder, anxiety, obsessive-compulsive disorder (OCD), eating disorders, and attention deficit hyperactivity disorder (ADHD). Studies suggest that these conditions may be related to inefficient processing of information in the prefrontal cortex. As with schizophrenia, however, many factors play a part in determining the risk of these complex disorders.

Where is the COMT gene located?

Cytogenetic Location: 22q11.21

Molecular Location on chromosome 22: base pairs 19,941,739 to 19,969,974

The COMT gene is located on the long (q) arm of chromosome 22 at position 11.21.

The COMT gene is located on the long (q) arm of chromosome 22 at position 11.21.

More precisely, the COMT gene is located from base pair 19,941,739 to base pair 19,969,974 on chromosome 22.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about COMT?

You and your healthcare professional may find the following resources about COMT helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the COMT gene or gene products?

  • Catechol Methyltransferase
  • COMT_HUMAN

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding COMT?

ADHD ; amino acid ; anxiety ; attention deficit hyperactivity disorder ; bipolar disorder ; cell ; chromosome ; cognition ; deletion ; depression ; dopamine ; enzyme ; gene ; hyperactivity ; Mb ; mental illness ; methionine ; methyltransferase ; nerve cell ; neurotransmitters ; obsessive-compulsive disorder ; OCD ; panic disorder ; polymorphism ; prefrontal cortex ; protein ; schizophrenia ; soluble ; syndrome ; thermolabile ; valine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Baker K, Baldeweg T, Sivagnanasundaram S, Scambler P, Skuse D. COMT Val108/158 Met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome. Biol Psychiatry. 2005 Jul 1;58(1):23-31. (http://www.ncbi.nlm.nih.gov/pubmed/15935994?dopt=Abstract)
  • Bearden CE, Jawad AF, Lynch DR, Monterossso JR, Sokol S, McDonald-McGinn DM, Saitta SC, Harris SE, Moss E, Wang PP, Zackai E, Emanuel BS, Simon TJ. Effects of COMT genotype on behavioral symptomatology in the 22q11.2 Deletion Syndrome. Child Neuropsychol. 2005 Feb;11(1):109-17. (http://www.ncbi.nlm.nih.gov/pubmed/15846854?dopt=Abstract)
  • Bearden CE, Jawad AF, Lynch DR, Sokol S, Kanes SJ, McDonald-McGinn DM, Saitta SC, Harris SE, Moss E, Wang PP, Zackai E, Emanuel BS, Simon TJ. Effects of a functional COMT polymorphism on prefrontal cognitive function in patients with 22q11.2 deletion syndrome. Am J Psychiatry. 2004 Sep;161(9):1700-2. (http://www.ncbi.nlm.nih.gov/pubmed/15337663?dopt=Abstract)
  • Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet. 2004 Nov;75(5):807-21. Epub 2004 Sep 27. Erratum in: Am J Hum Genet. 2005 Jun;76(6):1089. (http://www.ncbi.nlm.nih.gov/pubmed/15457404?dopt=Abstract)
  • Craddock N, Owen MJ, O'Donovan MC. The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol Psychiatry. 2006 May;11(5):446-58. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16505837?dopt=Abstract)
  • Fan JB, Zhang CS, Gu NF, Li XW, Sun WW, Wang HY, Feng GY, St Clair D, He L. Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biol Psychiatry. 2005 Jan 15;57(2):139-44. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15652872?dopt=Abstract)
  • Glaser B, Debbane M, Hinard C, Morris MA, Dahoun SP, Antonarakis SE, Eliez S. No evidence for an effect of COMT Val158Met genotype on executive function in patients with 22q11 deletion syndrome. Am J Psychiatry. 2006 Mar;163(3):537-9. (http://www.ncbi.nlm.nih.gov/pubmed/16513880?dopt=Abstract)
  • Glatt SJ, Faraone SV, Tsuang MT. Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies. Am J Psychiatry. 2003 Mar;160(3):469-76. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12611827?dopt=Abstract)
  • Gothelf D, Eliez S, Thompson T, Hinard C, Penniman L, Feinstein C, Kwon H, Jin S, Jo B, Antonarakis SE, Morris MA, Reiss AL. COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome. Nat Neurosci. 2005 Nov;8(11):1500-2. Epub 2005 Oct 23. (http://www.ncbi.nlm.nih.gov/pubmed/16234808?dopt=Abstract)
  • Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry. 2005 Jan;10(1):40-68; image 5. Review. Erratum in: Mol Psychiatry. 2005 Apr;10(4):420. Mol Psychiatry. 2005 Aug;10(8):804. (http://www.ncbi.nlm.nih.gov/pubmed/15263907?dopt=Abstract)
  • Meyer-Lindenberg A, Nichols T, Callicott JH, Ding J, Kolachana B, Buckholtz J, Mattay VS, Egan M, Weinberger DR. Impact of complex genetic variation in COMT on human brain function. Mol Psychiatry. 2006 Sep;11(9):867-77, 797. Epub 2006 Jun 20. (http://www.ncbi.nlm.nih.gov/pubmed/16786032?dopt=Abstract)
  • Mikołajczyk E, Smiarowska M, Grzywacz A, Samochowiec J. Association of eating disorders with catechol-o-methyltransferase gene functional polymorphism. Neuropsychobiology. 2006;54(1):82-6. Epub 2006 Oct 5. (http://www.ncbi.nlm.nih.gov/pubmed/17028449?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1312)
  • Savitz J, Solms M, Ramesar R. The molecular genetics of cognition: dopamine, COMT and BDNF. Genes Brain Behav. 2006 Jun;5(4):311-28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16716201?dopt=Abstract)
  • Shashi V, Keshavan MS, Howard TD, Berry MN, Basehore MJ, Lewandowski E, Kwapil TR. Cognitive correlates of a functional COMT polymorphism in children with 22q11.2 deletion syndrome. Clin Genet. 2006 Mar;69(3):234-8. (http://www.ncbi.nlm.nih.gov/pubmed/16542388?dopt=Abstract)
  • Shifman S, Bronstein M, Sternfeld M, Pisanté A, Weizman A, Reznik I, Spivak B, Grisaru N, Karp L, Schiffer R, Kotler M, Strous RD, Swartz-Vanetik M, Knobler HY, Shinar E, Yakir B, Zak NB, Darvasi A. COMT: a common susceptibility gene in bipolar disorder and schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128B(1):61-4. (http://www.ncbi.nlm.nih.gov/pubmed/15211633?dopt=Abstract)
  • Simon TJ, Bish JP, Bearden CE, Ding L, Ferrante S, Nguyen V, Gee JC, McDonald-McGinn DM, Zackai EH, Emanuel BS. A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children. Dev Psychopathol. 2005 Summer;17(3):753-84. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16262991?dopt=Abstract)
  • Williams HJ, Glaser B, Williams NM, Norton N, Zammit S, MacGregor S, Kirov GK, Owen MJ, O'Donovan MC. No association between schizophrenia and polymorphisms in COMT in two large samples. Am J Psychiatry. 2005 Sep;162(9):1736-8. (http://www.ncbi.nlm.nih.gov/pubmed/16135635?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2007
Published: September 15, 2014