OPEN ACCESS Jacobs Journal of Dentistry and Research Catechol O-Methyltransferase: A Review of the Gene and Enzyme Neil R. McGregor* Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia *Corresponding author: Dr. Neil McGregor, Faculty of Medicine, Dentistry and Health Sciences. University of Melbourne, 4A Wilm- ot Street, Malvern East 3145, Australia, Email: neilm@unimelb.edu.au Received: 05-23-2014 Accepted: 09-12-2014 Published: 09-15-2014 Copyright: © 2014 Neil Research Article Cite this article: Mc Gregor N R. Catechol O-Methyltransferase: A Review of the Gene and Enzyme. J J Dent Res. 2014. 1(1): 006. Abstract Genetic polymorphisms in the Catechol O-Methyltransferase (COMT) gene have been linked to increased pain sensitivity in a number of studies. A literature search was performed to integrate the current knowledge of the gene, its regulation, influ- ences of the polymorphisms upon enzyme function and its population distributions. Assessment also includes the current knowledge of the enzyme structure, isoforms, function and metabolic activities, substrates, and products. Other gene poly- morphisms which may influence the components involved within the COMT enzymatic reaction, such as folate metabolism polymorphisms and cofactor availability, were also briefly assessed. A review of enzyme agonists and antagonist and how these may influence the enzymes functions, its substrates and products is undertaken in an attempt to understand the po- tential interactions between COMT and factors that may influence enzyme activity in the presence or absence of the COMT polymorphic forms. Keywords: Catechol O-Methyltransferase; Monoamine Oxidase; Aldehyde Dehydrogenase; Polymorphism, Genetic; Pain; Temporomandibular disorders; Fatigue Syndrome, Chronic; Antagonists and Inhibitors; Agonists; Catecholamines; Oestro- gens; S-Adenosylmethionine: Alcohol Dehydrogenase; Aldosterone; Glucocorticoids Introduction Recent research has provided evidence that polymorphic forms of some genes may be involved in development and/or persistence the pain syndromes, such as temporomandibu- lar joint dysfunction (TMD), fibromyalgia and chronic fatigue syndrome (MECFS). From these data a series of intriguing relationships have been found between the slow reacting polymorphic forms of the enzyme Catechol O-Methyltrans- ferase (EC 2.1.1.6) (COMT) and pain. The slow forms have been reported to have an increased prevalence in subjects who have defined TMD [1-7], MECFS [8,9] and fibromyalgia [10, 11], but other studies have not confirmed these findings for MECFS or fibromyalgia [12-14] or localized pain syn- dromes as whole groups [15]. However the COMT gene has been found to be associated with a subgroup of MECFS pa- tients, in particular those with increases in depressive symp- toms [16]. Further studies are warranted to confirm or deny these initial observations. A series of mutations within the COMT gene sequence and its promoter region have been found to result in low enzyme activity [1, 6, 17, 18]. The crucial event seems to be the alter- ation in RNA/mRNA conversion or stability, which results in reduction in protein production and hence of total enzyme quantity and activity [17]. A recent study has shown that the instability of these altered COMT proteins is associated with the cellular environment; the higher the level of oxi- dation products the greater the reduction in COMT enzyme protein and activity [19]. Thus, a combination of genetic sus- ceptibility and environmental factors that increase oxidation by-products or result in higher oxidative damage may signifi- cantly alter the normal response to a challenge, particularly in subjects who carry the slow polymorphic forms of COMT.