Genomes and Genes
catechol o methyltransferase
Summary: Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.
- Michaelovsky E, Gothelf D, Korostishevsky M, Frisch A, Burg M, Carmel M, et al. Association between a common haplotype in the COMT gene region and psychiatric disorders in individuals with 22q11.2DS. Int J Neuropsychopharmacol. 2008;11:351-63 pubmed..2DS and supports the hypothesis that COMT gene variations contribute to genetic predisposition to psychiatric disorders in the general population. ..
- Montag C, Hartmann P, Merz M, Burk C, Reuter M. D2 receptor density and prepulse inhibition in humans: negative findings from a molecular genetic approach. Behav Brain Res. 2008;187:428-32 pubmed..Further molecular genetic studies investigating other variants on dopaminergic genes have to be conducted. ..
- Tan H, Chen Q, Goldberg T, Mattay V, Meyer Lindenberg A, Weinberger D, et al. Catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal brain systems during arithmetic and temporal transformations in working memory. J Neurosci. 2007;27:13393-401 pubmed..These findings add to the integration of dopaminergic signaling in basic cortical assemblies with their roles in specific human brain networks during the orchestration of information processing in WM. ..
- Zhu B, Shim J, Nagai M, Bai H. Molecular modelling study of the mechanism of high-potency inhibition of human catechol-O-methyltransferase by (-)-epigallocatechin-3-O-gallate. Xenobiotica. 2008;38:130-46 pubmed..It is concluded that the very tight binding interaction of EGCG with COMT makes it a potent non-competitive inhibitor, but its imperfect geometry makes it a poor substrate for methylation by this enzyme. ..
- Vargas Alarcon G, Fragoso J, Cruz Robles D, Vargas A, Vargas A, Lao Villadóniga J, et al. Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis Res Ther. 2007;9:R110 pubmed..This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results. ..
- Hintsanen M, Elovainio M, Puttonen S, Kivimaki M, Lehtimaki T, Kahonen M, et al. Val/Met polymorphism of the COMT gene moderates the association between job strain and early atherosclerosis in young men. J Occup Environ Med. 2008;50:649-57 pubmed publisher..Our findings support a general model in which the interaction between genotype and job strain is assumed to predispose to increased atherosclerotic processes. ..
- Salama S, Kamel M, Diaz Arrastia C, Xu X, Veenstra T, Salih S, et al. Effect of tumor necrosis factor-alpha on estrogen metabolism and endometrial cells: potential physiological and pathological relevance. J Clin Endocrinol Metab. 2009;94:285-93 pubmed publisher..These effects may impact many physiological and pathological processes that occur within the endometrium. ..
- Giakoumaki S, Roussos P, Bitsios P. Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism. Neuropsychopharmacology. 2008;33:3058-68 pubmed publisher..These results suggest that early information processing and working memory may both depend on PFC DA signaling, and that they may both relate to PFC DA levels according to an inverted U-shaped curve function. ..
- Puls I, Mohr J, Wrase J, Priller J, Behr J, Kitzrow W, et al. Synergistic effects of the dopaminergic and glutamatergic system on hippocampal volume in alcohol-dependent patients. Biol Psychol. 2008;79:126-36 pubmed publisher..These data are in line with prior studies supporting a role for dopamine-glutamate interaction in modulation of alcohol disease. ..
- Ross J, Riley J, Taegetmeyer A, Sato H, Gretton S, du Bois R, et al. Genetic variation and response to morphine in cancer patients: catechol-O-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects. Cancer. 2008;112:1390-403 pubmed publisher..The authors believe that this work adds significantly to the current understanding of genetic variants that may influence an individual's response to opioids. ..
- Papaleo F, Crawley J, Song J, Lipska B, Pickel J, Weinberger D, et al. Genetic dissection of the role of catechol-O-methyltransferase in cognition and stress reactivity in mice. J Neurosci. 2008;28:8709-23 pubmed publisher..Our data indicate a critical role for the COMT gene in an apparent evolutionary trade-off between cognitive and affective functions. ..
- Munafo M, Johnstone E, Guo B, Murphy M, Aveyard P. Association of COMT Val108/158Met genotype with smoking cessation. Pharmacogenet Genomics. 2008;18:121-8 pubmed publisher..Future large-scale studies will be required to afford sufficient power to simultaneously investigate the role of multiple genetic variants in treatment responses, and the effects of potential moderating variables on these associations. ..
- Hong J, Lee J, Chung S, Jung J, Yoo H, Chang S, et al. New functional single nucleotide polymorphism (Ala72Ser) in the COMT gene is associated with aggressive behavior in male schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:658-60 pubmed publisher..000069). Our study showed a highly significant association between a COMT haplotype of two functional SNPs and aggressive behavior in schizophrenia. ..
- Drabant E, Hariri A, Meyer Lindenberg A, Munoz K, Mattay V, Kolachana B, et al. Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation. Arch Gen Psychiatry. 2006;63:1396-406 pubmed
- Akisik E, Dalay N. Functional polymorphism of thymidylate synthase, but not of the COMT and IL-1B genes, is associated with breast cancer. J Clin Lab Anal. 2007;21:97-102 pubmed..On the other hand, the TS 1494del6 polymorphism is associated with a significantly lower risk of breast cancer and may be a potential genetic marker. ..
- Nackley A, Shabalina S, Tchivileva I, Satterfield K, Korchynskyi O, Makarov S, et al. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006;314:1930-3 pubmed..These data highlight the functional significance of synonymous variations and suggest the importance of haplotypes over single-nucleotide polymorphisms for analysis of genetic variations. ..
- Yavich L, Forsberg M, Karayiorgou M, Gogos J, Mannisto P. Site-specific role of catechol-O-methyltransferase in dopamine overflow within prefrontal cortex and dorsal striatum. J Neurosci. 2007;27:10196-209 pubmed
- Williams H, Owen M, O Donovan M. Is COMT a susceptibility gene for schizophrenia?. Schizophr Bull. 2007;33:635-41 pubmed
- Lu B, Martin K, Edgar J, Smith A, LEWIS S, Escamilla M, et al. Effect of catechol O-methyltransferase val(158)met polymorphism on the p50 gating endophenotype in schizophrenia. Biol Psychiatry. 2007;62:822-5 pubmed..Valine homozygous individuals are more likely to have gating deficits, supporting COMT as a genetic determinant of the P50 endophenotype, as well as a role for prefrontal dopamine in auditory filtering. ..
- Tunbridge E, Lane T, Harrison P. Expression of multiple catechol-o-methyltransferase (COMT) mRNA variants in human brain. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:834-9 pubmed..The alternate gene products may be of significant functional importance, and differentially impacted by polymorphisms within the COMT gene. ..
- Domschke K, Deckert J, O Donovan M, Glatt S. Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:667-73 pubmed
- Williams Gray C, Hampshire A, Robbins T, Owen A, Barker R. Catechol O-methyltransferase Val158Met genotype influences frontoparietal activity during planning in patients with Parkinson's disease. J Neurosci. 2007;27:4832-8 pubmed
- Frank M, Moustafa A, Haughey H, Curran T, Hutchison K. Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning. Proc Natl Acad Sci U S A. 2007;104:16311-6 pubmed..Computational maximum likelihood analyses reveal independent gene effects on three reinforcement learning parameters that can explain the observed dissociations. ..
- Hassan M, Salama S, Arafa H, Hamada F, Al Hendy A. Adenovirus-mediated delivery of a dominant-negative estrogen receptor gene in uterine leiomyoma cells abrogates estrogen- and progesterone-regulated gene expression. J Clin Endocrinol Metab. 2007;92:3949-57 pubmed
- Baud P, Courtet P, Perroud N, Jollant F, Buresi C, Malafosse A. Catechol-O-methyltransferase polymorphism (COMT) in suicide attempters: a possible gender effect on anger traits. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:1042-7 pubmed..These results are discussed in the light of recently published data on the effect of COMT Val158Met polymorphism on different cognitive and behavioral traits. ..
- Harrison P, Tunbridge E. Catechol-O-methyltransferase (COMT): a gene contributing to sex differences in brain function, and to sexual dimorphism in the predisposition to psychiatric disorders. Neuropsychopharmacology. 2008;33:3037-45 pubmed..Since sex differences in the genetic architecture of quantitative traits are the rule not the exception, we anticipate that additional evidence will emerge for sexual dimorphisms, not only in COMT but also in many other autosomal genes. ..
- Bertolino A, Caforio G, Blasi G, Rampino A, Nardini M, Weinberger D, et al. COMT Val158Met polymorphism predicts negative symptoms response to treatment with olanzapine in schizophrenia. Schizophr Res. 2007;95:253-5 pubmed
- Hagen K, Pettersen E, Stovner L, Skorpen F, Holmen J, Zwart J. High systolic blood pressure is associated with Val/Val genotype in the catechol-o-methyltransferase gene. The Nord-Trøndelag Health Study (HUNT). Am J Hypertens. 2007;20:21-6 pubmed..Based on the study findings, the Val/Val genotype appears to be associated with a higher prevalence of increased systolic BP compared with the Met/Met or Met/Val genotypes at the COMTgene. ..
- Wang S, Morton L, Bergen A, Lan E, Chatterjee N, Kvale P, et al. Genetic variation in catechol-O-methyltransferase (COMT) and obesity in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. Hum Genet. 2007;122:41-9 pubmed..Our results support a need for comprehensive evaluation of COMT variations and their functional relevance as COMT may be an important molecular target to evaluate for new treatments regarding obesity. ..
- Wen W, Ren Z, Shu X, Cai Q, Ye C, Gao Y, et al. Expression of cytochrome P450 1B1 and catechol-O-methyltransferase in breast tissue and their associations with breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16:917-20 pubmed..These results support the hypothesis that the formation and accumulation of catechol estrogens in breast tissue through increased CYP1B1 expression and reduced COMT expression may play a significant role in breast cancer risk. ..
- Grice D, Reenilä I, Mannisto P, Brooks A, Smith G, Golden G, et al. Transcriptional profiling of C57 and DBA strains of mice in the absence and presence of morphine. BMC Genomics. 2007;8:76 pubmed
- Tan H, Chen Q, Sust S, Buckholtz J, Meyers J, Egan M, et al. Epistasis between catechol-O-methyltransferase and type II metabotropic glutamate receptor 3 genes on working memory brain function. Proc Natl Acad Sci U S A. 2007;104:12536-41 pubmed..These findings extend putative brain dopaminergic and glutamatergic relationships indexed by COMT and GRM3 to a systems-level interaction in human cortical circuits implicated in working memory dysfunction such as in schizophrenia. ..
- Bai H, Shim J, Yu J, Zhu B. Biochemical and molecular modeling studies of the O-methylation of various endogenous and exogenous catechol substrates catalyzed by recombinant human soluble and membrane-bound catechol-O-methyltransferases. Chem Res Toxicol. 2007;20:1409-25 pubmed..Also, our modeling data precisely predicted the regioselectivity for the O-methylation of these substrates at different hydroxyl groups, the predicted values matched nearly perfectly with the experimental data. ..
- Jabbi M, Kema I, van der Pompe G, Te Meerman G, Ormel J, den Boer J. Catechol-o-methyltransferase polymorphism and susceptibility to major depressive disorder modulates psychological stress response. Psychiatr Genet. 2007;17:183-93 pubmed
- Wichers M, Aguilera M, Kenis G, Krabbendam L, Myin Germeys I, Jacobs N, et al. The catechol-O-methyl transferase Val158Met polymorphism and experience of reward in the flow of daily life. Neuropsychopharmacology. 2008;33:3030-6 pubmed..Genetic moderation of ecological measures of reward experience is hypothesized to be of major relevance to the development of various behavioral disorders, including depression and addiction. ..
- Hosak L. Role of the COMT gene Val158Met polymorphism in mental disorders: a review. Eur Psychiatry. 2007;22:276-81 pubmed..Gene-gene and gene-environment interactions should also be considered. The COMT gene is probably not "a gene for" any mental disorder, but the Val158Met polymorphism appears to have pleiotropic effects on human behavior. ..
- Sei Y, Ren Patterson R, Li Z, Tunbridge E, Egan M, Kolachana B, et al. Neuregulin1-induced cell migration is impaired in schizophrenia: association with neuregulin1 and catechol-o-methyltransferase gene polymorphisms. Mol Psychiatry. 2007;12:946-57 pubmed
- van Amelsvoort T, Zinkstok J, Figee M, Daly E, Morris R, Owen M, et al. Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome. Psychol Med. 2008;38:89-100 pubmed..COMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS. ..
- Burdick K, Funke B, Goldberg J, Bates J, Jaeger J, Kucherlapati R, et al. COMT genotype increases risk for bipolar I disorder and influences neurocognitive performance. Bipolar Disord. 2007;9:370-6 pubmed..32) or cognition in our sample. These data suggest that COMT genetic variation at SNP rs165599 is associated with BPD I and influences prefrontal aspects of verbal memory in bipolar patients and healthy controls. ..
- Starr J, Fox H, Harris S, Deary I, Whalley L. COMT genotype and cognitive ability: a longitudinal aging study. Neurosci Lett. 2007;421:57-61 pubmed..I. 34.3-35.5), and Met/Met 34.9 (95% C.I. 34.1-35.8). This study adds to the evidence that the Val/Val polymorphism has a detrimental effect on cognition, extending upwards the age range in which such an effect has been detected. ..
- Buckholtz J, Sust S, Tan H, Mattay V, Straub R, Meyer Lindenberg A, et al. fMRI evidence for functional epistasis between COMT and RGS4. Mol Psychiatry. 2007;12:893-5, 885 pubmed
- Straub R, Lipska B, Egan M, Goldberg T, Callicott J, Mayhew M, et al. Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression. Mol Psychiatry. 2007;12:854-69 pubmed..These coincident results implicate GAD1 in the etiology of schizophrenia and suggest that the mechanism involves altered cortical GABA inhibitory activity, perhaps modulated by dopaminergic function. ..
- Muntjewerff J, Gellekink H, den Heijer M, Hoogendoorn M, Kahn R, Sinke R, et al. Polymorphisms in catechol-O-methyltransferase and methylenetetrahydrofolate reductase in relation to the risk of schizophrenia. Eur Neuropsychopharmacol. 2008;18:99-106 pubmed..017). Our findings do not support a major role for the COMT 324AA and MTHFR 677TT genotype alone, but the combination of both genotypes might increase schizophrenia susceptibility. ..
- Barnett J, Jones P, Robbins T, Muller U. Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls. Mol Psychiatry. 2007;12:502-9 pubmed..There was no evidence of publication bias. We conclude that there is small but significant relationship between Val(158)Met genotype and executive function in healthy individuals but not in schizophrenia. ..
- Zeng B, Balfour R, Jackson M, Rose S, Jenner P. Expression of catechol-O-methyltransferase in the brain and periphery of normal and MPTP-treated common marmosets. J Neural Transm (Vienna). 2010;117:45-51 pubmed publisher..COMT activity appears unaffected by loss of the dopaminergic nigro-striatal pathway and levodopa treatment. ..
- Kang J, Namkoong K, Ha R, Jhung K, Kim Y, Kim S. Influence of BDNF and COMT polymorphisms on emotional decision making. Neuropharmacology. 2010;58:1109-13 pubmed publisher..No interaction effect was observed between the BDNF and the COMT for the IGT. These findings suggest the BDNF Val66Met may affect the emotional decision making performance. ..
- Frank M, Doll B, Oas Terpstra J, Moreno F. Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation. Nat Neurosci. 2009;12:1062-8 pubmed publisher..Quantitative model fits reveal that genetic factors modulate independent parameters of a reinforcement learning system. ..
- Huehne K, Leis S, Muenster T, Wehrfritz A, Winter S, Maihofner C, et al. High post surgical opioid requirements in Crohn's disease are not due to a general change in pain sensitivity. Eur J Pain. 2009;13:1036-42 pubmed publisher..The results indicate that a more complex pathway is involved in the greater post operative opioid demand in CD. Therefore the presence of other, as yet unknown, genes could modulate opioid requirements in CD patients. ..
- Shrubsole M, Lu W, Chen Z, Shu X, Zheng Y, Dai Q, et al. Drinking green tea modestly reduces breast cancer risk. J Nutr. 2009;139:310-6 pubmed publisher..046). COMT rs4680 genotypes did not have a modifying effect on the association of green tea intake with breast cancer risk. Drinking green tea may be weakly associated with a decreased risk of breast cancer. ..
- Williams J, Andersson T, Andersson T, Blanchard R, Behm M, Cohen N, et al. PhRMA white paper on ADME pharmacogenomics. J Clin Pharmacol. 2008;48:849-89 pubmed publisher..In addition, the paper includes a brief review on the clinically relevant genetic variants of drug-metabolizing enzymes and transporters most relevant to the pharmaceutical industry. ..
- Albaugh M, Harder V, Althoff R, Rettew D, Ehli E, Lengyel Nelson T, et al. COMT Val158Met genotype as a risk factor for problem behaviors in youth. J Am Acad Child Adolesc Psychiatry. 2010;49:841-9 pubmed publisher..062). After controlling for demographics, SES, and maternal parenting quality as confounders, there remains a strong association between youth carrying a Met allele and higher average AGG scores relative to Val-homozygotes. ..
- Lee H, Kim Y. Catechol-O-methyltransferase Val158Met polymorphism affects therapeutic response to mood stabilizer in symptomatic manic patients. Psychiatry Res. 2010;175:63-6 pubmed publisher..Further studies with a larger number of subjects and well-controlled design will be required to better understand the role of the COMT gene polymorphism on the therapeutic response to mood stabilizer in manic patients. ..
- Roffman J, Weiss A, Deckersbach T, Freudenreich O, Henderson D, Wong D, et al. Interactive effects of COMT Val108/158Met and MTHFR C677T on executive function in schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:990-5 pubmed publisher..It is plausible that cumulative effects of the MTHFR T and COMT Val alleles on intracellular methylation profiles and prefrontal dopamine transmission underlie their interactive effect on perseverative errors. ..