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COMT gene
URL of this page: https://medlineplus.gov/genetics/gene/comt/

COMT gene

catechol-O-methyltransferase

Normal Function

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 signaling by neurotransmitters such as dopamine and norepinephrine. Catechol-O-methyltransferase helps maintain appropriate levels of these neurotransmitters in this part of the brain.

Health Conditions Related to Genetic Changes

22q11.2 deletion syndrome

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.

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Other disorders

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.

Other Names for This Gene

  • Catechol Methyltransferase
  • COMT_HUMAN

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

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. doi: 10.1016/j.biopsych.2005.03.020. Citation on PubMed
  • 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. doi: 10.1080/09297040590911239. Citation on PubMed or Free article on PubMed Central
  • 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. doi: 10.1176/appi.ajp.161.9.1700. Citation on PubMed
  • 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. doi: 10.1086/425589. Epub 2004 Sep 27. Erratum In: Am J Hum Genet. 2005 Jun;76(6):1089. Citation on PubMed or Free article on PubMed Central
  • 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. doi: 10.1038/sj.mp.4001808. Citation on PubMed
  • 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. doi: 10.1016/j.biopsych.2004.10.018. Citation on PubMed
  • 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. doi: 10.1176/appi.ajp.163.3.537. Citation on PubMed
  • 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. doi: 10.1176/appi.ajp.160.3.469. Citation on PubMed
  • 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. doi: 10.1038/nn1572. Epub 2005 Oct 23. Citation on PubMed
  • 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. doi: 10.1038/sj.mp.4001558. Erratum In: Mol Psychiatry. 2005 Apr;10(4):420. Mol Psychiatry. 2005 Aug;10(8):804. Citation on PubMed
  • 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. doi: 10.1038/sj.mp.4001860. Epub 2006 Jun 20. Citation on PubMed
  • Mikolajczyk E, Smiarowska M, Grzywacz A, Samochowiec J. Association of eating disorders with catechol-o-methyltransferase gene functional polymorphism. Neuropsychobiology. 2006;54(1):82-6. doi: 10.1159/000096043. Epub 2006 Oct 5. Citation on PubMed
  • Savitz J, Solms M, Ramesar R. The molecular genetics of cognition: dopamine, COMT and BDNF. Genes Brain Behav. 2006 Jun;5(4):311-28. doi: 10.1111/j.1601-183X.2005.00163.x. Citation on PubMed
  • 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. doi: 10.1111/j.1399-0004.2006.00569.x. Citation on PubMed
  • Shifman S, Bronstein M, Sternfeld M, Pisante 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. doi: 10.1002/ajmg.b.30032. Citation on PubMed
  • 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. doi: 10.1017/S0954579405050364. Citation on PubMed or Free article on PubMed Central
  • 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. doi: 10.1176/appi.ajp.162.9.1736. Citation on PubMed

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