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1

&NA;. "COMT inhibitors." Inpharma Weekly &NA;, no. 1135 (May 1998): 6. http://dx.doi.org/10.2165/00128413-199811350-00009.

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Meloto, Carolina B., Samantha K. Segall, Shad Smith, Marc Parisien, Svetlana A. Shabalina, Célia M. Rizzatti-Barbosa, Josée Gauthier, et al. "COMT gene locus." PAIN 156, no. 10 (October 2015): 2072–83. http://dx.doi.org/10.1097/j.pain.0000000000000273.

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O’Tuathaigh, Colm. "S.12.2 - COMT." Behavioural Pharmacology 24 (October 2013): e15. http://dx.doi.org/10.1097/01.fbp.0000434735.74603.db.

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Papaleo, F., M. C. Burdick, J. H. Callicott, and D. R. Weinberger. "COMT–Dysbindin epistatic interaction." Molecular Psychiatry 19, no. 3 (February 21, 2014): 273. http://dx.doi.org/10.1038/mp.2014.6.

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Adler, Charles H. "COMT Inhibitors: Novel Treatments for Parkinson's Disease." CNS Spectrums 3, no. 2 (February 1998): 53–56. http://dx.doi.org/10.1017/s109285290000554x.

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AbstractCatechol-O-methyltransferase (COMT) inhibitors are a new class of medication being developed for the treatment of Parkinson's disease (PD). The enzyme COMT metabolizes levodopa and dopamine, both peripherally and centrally. Coadministration of a COMT inhibitor with levodopa creates an increase in peripheral and central levodopa bioavailability, as well as higher central dopamine concentrations. Because these actions improve the duration of response to levodopa, the COMT inhibitors should prove to be useful adjunctive therapies in PD patients.
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Wang, Ruike, Sai Li, Xiuhai Wang, Dan Wu, Peng Yang, Qifeng Yin, Yujuan Wang, and Shiguo Liu. "Association between COMT -287A/G (rs2075507) polymorphism and preeclampsia in a Chinese Han population." International Journal of Sciences Volume 5, no. 2016-03 (April 3, 2016): 137–42. https://doi.org/10.5281/zenodo.3349151.

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Previous study indicated that COMT might play a significant role in the development of preeclampsia(PE). The purpose of our study is to investigate the association of COMT -287A/G polymorphism (rs2075507) with PE susceptibility in Chinese han population. 505 PE patients and 824 normal pregnant women were enrolled in our research. All the subjects were detected the genotype of COMT -287 loci by Polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) method. Demographics and clinical data were performed using t test or Mann-Whitney test. The frequencies of the allelic and genotypic distribution between PE patients and healthy controls were analyzed by X2 test. No significant difference in the genotypic distribution was found between the patients and controls (x2 =0.13, p=0.94), while frequency of the allele showed a unstatistical significant difference (x2=0.07, p=0.79). The COMT -287A/G polymorphism might be associated with the PE in Chinese women. Further researches are yet needed to validate the relationship between the COMT -287A/G and the PE in different ethnic groups.Read Complete Article at ijSciences: V5201603987 AND DOI: http://dx.doi.org/10.18483/ijSci.987
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Zammit, Stanley, Michael J. Owen, Jonathan Evans, Jon Heron, and Glyn Lewis. "Cannabis, COMT and psychotic experiences." British Journal of Psychiatry 199, no. 5 (November 2011): 380–85. http://dx.doi.org/10.1192/bjp.bp.111.091421.

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BackgroundA putative interaction between cannabis and variation at rs4680 within the catechol-methyl-transferase (COMT) gene on psychosis has been reported, but not adequately replicated.AimsTo examine whether the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT.MethodA longitudinal study of 2630 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who completed questionnaire-based assessments for cannabis use at age 14 and incident psychotic experiences at age 16. Six SNPs within COMT were genotyped.ResultsThere was no evidence of an interaction under multiplicative models between cannabis use and COMT on the risk of developing psychotic experiences in our primary analyses. In sensitivity analyses we observed highly variable evidence of interaction, whereby psychotomimetic effects of cannabis were greater in methionine homozygotes under some scenarios, but in valine homozygotes under others.ConclusionsCannabis increases risk of psychosis irrespective of underlying COMT genotypes. These findings argue against the widely held belief that the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT. The public health message about the potential increase in risk of psychotic disorders following cannabis use should not be tempered by reports that this harm is subgroup specific in the absence of robust evidence of replication.
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Jiao, Meng, Christopher J. Pirozzi, Chen Yu, Xuhui Bao, Mengjie Hu, Dong Pan, Sejiro Littleton, et al. "Abstract LB280: Enhancing glioblastoma radiotherapy by COMT inhibition." Cancer Research 84, no. 7_Supplement (April 5, 2024): LB280. http://dx.doi.org/10.1158/1538-7445.am2024-lb280.

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Abstract There is an urgent unmet medical need to discover novel therapeutics to enhance the efficacy of glioma radiotherapy. Here we assessed the roles of catechol - o - methyltransferase COMT, a key enzyme in dopamine metabolism and a drug target for Parkinson's disease, in glioma treatment. Analysis of TCGA data showed significantly higher COMT expression levels in glioma versus normal brain tissues. Inhibition of COMT by genetic knockout or FDA - approved COMT inhibitors significantly sensitized glioma cells to radiotherapy in vitro and murine glioma in vivo. Mechanistically, COMT inhibition in glioblastoma cells led to mitochondria dysfunction and increased mitochondrial RNA release into the cytoplasm, activating the cellular antiviral dsRNA sensing pathway and type I IFN response. Elevated type I IFNs stimulated microglial cells′ phagocytic capacity, enhancing radiotherapy efficacy. Because of the long - established safety record of the COMT inhibitors, our findings provide a solid rationale to evaluate them in combination with radiotherapy in glioma patients. Citation Format: Meng Jiao, Christopher J. Pirozzi, Chen Yu, Xuhui Bao, Mengjie Hu, Dong Pan, Sejiro Littleton, Nathan Reynolds, Daniel R. Saban, Fang Li, Chuan-yuan Li. Enhancing glioblastoma radiotherapy by COMT inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB280.
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9

Semen, M. O., O. L. Lychkovska, I. E. Shymanska, V. D. Semen, and H. V. Makukh. "High frequency of the 472AA COMT (Val158) homozygous genotype of the catechol-O-methyltransferase (COMT) gene in children with irritable bowel syndrome." Modern pediatrics. Ukraine, no. 6(126) (October 29, 2022): 23–29. http://dx.doi.org/10.15574/sp.2022.126.23.

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Following the biopsychosocial model of medicine, the pathophysiological basis of irritable bowel syndrome (IBS) is a combination of biological, psychoemotional, and psychosocial factors, the contribution of each of them to the development of this disorder remains unclear. Psychoemotinal factors, which are involved in the pathogenesis of IBS, are caused not only by the environment but also by the metabolism of catecholamines, particularly by the functional activity of catechol-O-methyltransferase (COMT). Purpose - to determine the role of Val158Met COMT polymorphism in development of IBS in children; to identify associations between genotype and clinical variant of the disorder and the nature of the provoking factor. Materials and methods. The material for the molecular genetic study were DNA samples obtained from nuclear cells of venous blood of 54 patients aged 6-12 years with diagnosed IBS. In 48 practically healthy children of the same age DNA samples were isolated from buccal epithelial cells. Molecular genetic study of single nucleotide polymorphism rs4680 of COMT gene was performed by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Microsoft Excel 2016 and GraphPad Prism 5 software were used for statistical analysis. Results. We have revealed significant differences in the distribution of Val158Met COMT genotypes in children with IBS in comparison with the control group. There was established that the 472GА COMT is more prevalent in healthy children and has a protective role in the development of IBS. In contrast, homozygous genotypes 472GG and 472AA, which are associated with changes in functional activity of enzyme COMT, may be considered as the risk factors for IBS (p≤0.0001). Conclusions. Genotype 472АА COMT was mostly detected in сhildren with stress-associated IBS, which is more related to dysnociception, disorders of cognition, and emotional disturbances. The higher prevalence of 472GA COMT heterozygotes among children with postinfectious IBS and IBS associated with antibiotic therapy indicates a less important role for the psychoemotional component and nociceptive disorders in the onset of this disorder (p=0.03). The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.
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10

Belfer, I., and S. Segall. "COMT genetic variants and pain." Drugs of Today 47, no. 6 (2011): 457. http://dx.doi.org/10.1358/dot.2011.47.6.1611895.

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Martinez-Martin, P., and C. F. O'Brien. "Extending levodopa action: COMT inhibition." Neurology 50, Issue 6, Supplement 6 (June 1, 1998): S27—S32. http://dx.doi.org/10.1212/wnl.50.6_suppl_6.s27.

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Dorflinger, E., G. Magni, and F. Hoffmann. "COMT inhibition and Parkinson's disease." European Neuropsychopharmacology 8 (November 1998): S87—S88. http://dx.doi.org/10.1016/s0924-977x(98)80057-6.

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Buckley, P. F. "Cannabis, COMT and psychotic experiences." Yearbook of Psychiatry and Applied Mental Health 2013 (January 2013): 384. http://dx.doi.org/10.1016/j.ypsy.2012.07.004.

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Abi-Dargham, Anissa, J. Ekelund, B. Kolachana, G. Frankle, R. Narendran, D. Martinez, M. Slifstein, D. Weinberger, and M. Laruelle. "Cortical D1 across COMT genotypes." NeuroImage 31 (January 2006): T40. http://dx.doi.org/10.1016/j.neuroimage.2006.04.030.

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Rivest, Jean, C. Lynn Barclay, and Oksana Suchowersky. "COMT Inhibitors in Parkinson's Disease." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 26, S2 (August 1999): S34—S38. http://dx.doi.org/10.1017/s031716710000007x.

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The COMT inhibitors, tolcapone and entacapone, are a new class of Parkinson's medications. By inhibiting the enzyme catechol-o-methyl-transferase (COMT), they prevent peripheral degradation of levodopa, allowing a higher concentration to cross the blood-brain barrier. Pharmacokinetic studies have shown that both tolcapone and entacapone significantly prolong the elimination half life, and increase the area under the curve of levodopa without increasing C max. Clinical studies with COMT inhibitors have shown benefit in both stable and fluctuating PD patients with improvement in motor function with lower levodopa doses. Fluctuating patients also had increased “on” time and reduced “wearing off”. Side effects were most commonly related to increased dopaminergic stimulation. Specific side effects included diarrhea and elevated liver enzymes. The recent reports of three cases of fulminant hepatitis with the use of tolcapone has led many countries to remove this compound from their market. Concerns about a possible class effect should impose close monitoring of liver function tests with the use of any of the nitrocatechols.
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Arboleya, Luis. "COMT Gene Polymorphisms and Fibromyalgia." Reumatología Clínica (English Edition) 3, no. 1 (January 2007): 48–49. http://dx.doi.org/10.1016/s2173-5743(07)70209-5.

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Reichmann, Heinz. "Opicapon: ein neuer COMT-Hemmer." InFo Neurologie & Psychiatrie 19, no. 5 (May 2017): 18–19. http://dx.doi.org/10.1007/s15005-017-2173-6.

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Baier, Monika, Ekkehard Haen, and Peter Lauer. "COMT-Polymorphismus und GST-Mangel." NeuroTransmitter 24, no. 4 (April 2013): 49–52. http://dx.doi.org/10.1007/s15016-013-0140-0.

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Smith, Shad B., Ilkka Reenilä, Pekka T. Männistö, Gary D. Slade, William Maixner, Luda Diatchenko, and Andrea G. Nackley. "Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain." Pain 155, no. 11 (November 2014): 2390–99. http://dx.doi.org/10.1016/j.pain.2014.09.009.

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Silva, Anderson Matheus Pereira da, Victoria Brito Evangelista, Ilan Iginio da Silva, Vinícius Pereira da Silva, Vinícios Silveira Mendes, Ikaro Alves de Andrade, José Wilson Cosme de Mesquita Júnior, et al. "IDENTIFICAÇÃO E CARACTERIZAÇÃO POLIMÓRFICA DA CATECOL-O-METILTRANSFERASE (COMT): UMA REVISÃO DA LITERATURA." Centro de Pesquisas Avançadas em Qualidade de Vida 16, V16N2 (2024): 1. http://dx.doi.org/10.36692/v16n2-53r.

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A enzima catecol-O-metiltransferase (COMT) desempenha um papel crucial no metabolismo das catecolaminas, neurotransmissores essenciais para diversas funções cerebrais e periféricas.Objetivo: Este artigo aborda a importância da COMT, destacando sua relevância no tratamento de doenças neurodegenerativas e psiquiátricas, bem como sua associação com variações genéticas, especialmente o polimorfismo Val158Met. Metodologia: Através de uma revisão abrangente da literatura, são discutidos aspectos como a estrutura e função da COMT, os efeitos de inibidores da enzima, como tolcapona e entacapona, e as implicações das variações genéticas na resposta terapêutica e predisposição a distúrbios psiquiátricos. Resultados e discussão:Destaca-se a importância da farmacogenômica na personalização do tratamento para doenças neuropsiquiátricas e neurodegenerativas. Conclusão: Conclui-se que a pesquisa contínua sobre a COMT é essencial para desenvolver terapias mais eficazes e estratégias de tratamento personalizadas, visando otimizar os cuidados para os pacientes afetados por essas condições.
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Hamongan Nasution, Akhyar, and Aznan Lelo. "CATECHOL-O-METHYLTRANSFERASE (COMT) ENZYME LEVELS IN PATIENTS WITH PREOPERATIVE ANXIETY." PHARMACOLOGY, MEDICAL REPORTS, ORTHOPEDIC, AND ILLNESS DETAILS (COMORBID) 1, no. 1 (January 10, 2022): 33–40. http://dx.doi.org/10.55047/comorbid.v1i1.37.

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 The preoperative anxiety’s incidence is very high and mostly preoperative patients have anxiety. It was found that low COMT levels indicate a tendency to develop anxiety. Hence, this study aims to investigate COMT enzyme levels in patients with preoperative anxiety. This research is a purely experimental research with a pretest-posttest control group design and double-blind. Measurement of COMT enzyme levels was executed by utilizing ELISA technique. Blood samples were taken from preoperative anxiety patients who were assessed with the Amsterdam Preoperative Anxiety Information Scale (APAIS). The research was carried out at Haji Adam Malik General Hospital and Regional General Hospital dr. Pirngadi Medan, and Integrated Laboratory of the Faculty of Medicine, University of North Sumatra. The were 64 samples involved in this research that fit the inclusion and exclusion criteria. The findings show that COMT levels in the anxiety and control groups had differences with p values ​​= 0.014. In addition, COMT levels in the preoperative anxiety group were lower when compared to those without the preoperative anxiety group, where in the anxiety group had COMT enzyme levels of 0,14 ± 0,08 ng/dl, while in the control group had higher COMT levels 0,96 ± 1,11 ng/dl. The results showed that patients with preoperative anxiety had lower levels of the COMT enzyme compared to patients without preoperative anxiety. Researchers suspect there is a role for the COMT enzyme in causing preoperative anxiety.
 
 
 
 
 
 
 
 
 
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Rosli, Norsuhaila Rosmimi, Tengku Shahrul Anuar engku Ahmad Basri, Mohd Ilham Adenan, Roziah Mohd Janor, Rohana Ahmad, Lay Kek Teh, Mohd Zaki Salleh, Sahol Hamid Abu Bakar, and Richard Johari James. "Association of COMT Polymorphism and Academic Achievement among Female Undergraduate Students." Science Letters 15, no. 2 (June 15, 2021): 90–101. http://dx.doi.org/10.24191/sl.v15i2.13831.

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Academic achievement may be influenced by catechol-O-methyltransferase (COMT) polymorphism. A common functional polymorphism of COMT, the rs4680 is consistently being involved in the modulation of dopaminergic pathway and prefrontal cortex function which may predominantly affect cognitive functions. A total of 197 female participants were recruited in this study. The score of student’s grade point average (GPA) from the latest previous semester was used as the measurement of academic achievement. The COMT polymorphism was genotyped using tetra primer allele specific polymerase chain reaction. The findings indicated that there were 8 (4.1 %), 72 (36.5 %), and 117 (59.4 %) participants harbouring Met/Met, Met/Val, and Val/Val genotype for COMT polymorphism respectively. All the genotype distributions of COMT polymorphism were consistent with Hardy-Weinberg equilibrium (χ2 = 0.495, p > 0.05). The one-way analysis of variance (ANOVA) result demonstrated that participants bearing Met/Met genotype had a better achievement in GPA as compared to the other COMT genotypes (p = 0.001). These findings support evidence that the affective role of COMT polymorphism might overwhelm cognitive abilities in measures of academic achievement like GPA.
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Hamonangan Nasution, Akhyar, and Aznan Lelo. "Catechol-O-Methyltransferase (COMT) Enzyme Level In Preoperative Anxiety Patients." Journal of Society Medicine 1, no. 1 (October 8, 2022): 25–30. http://dx.doi.org/10.47353/jsocmed.v1i1.5.

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Background: Incidence of perioperative anxiety is very high, many preoperative patient experience anxiety . Thiamine acts as an essential nutrition funtionate as cofactor enzyme in most of mitochondria in brain. Brain is very susceptible to thiamine deficiency because its dependency on mitochondrial ATP production. Decreased ATP production result in inhibition of COMT activity. Low COMT levels indicated tendency for anxiety. The aim of this study is to determine the effect of thiamine in increasing COMT enzyme levels in patient with preoperative anxiety
 Methods : A true experiment with pretest-posttest control group and double-blind design conducted at the Department of Anesthesia and Intensive Care of University of North Sumatra in August 2019. The 60 patients were analyzed which were planned for and done an elective surgery under general anesthesia. Preoperative anxiety was measured with Amsterdam Preoperative Anxiety and Information Scale (APAIS) and COMT enzyme level measured by ELISA assays. 
 Results : The results showed that from 64 patients had incidence of preoperative anxiety in this study was 48.3%. We found that there is significant differences in COMT enzyme levels in thiamine group compared to control (p value = 0.001). In addition, it was seen that in thiamine group had an increased COMT levels from 0.96 ng/dL to 1.78 ng/dL, while in control group there also slight increasing from 0.44 ng/dL to 0.78 ng/dL. This show that increase in COMT levels is greater in thiamine group than control group. 
 Conclusion : Thiamine can cause increasing COMT enzyme levels in patients scheduled for elective surgery with preoperative anxiety under general anesthesia
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Kim, Jin-Hee, Jimin Lee, Hyesoo Jeong, Mi Seo Bang, Jin-Hyun Jeong, and Minsun Chang. "Nordihydroguaiaretic Acid as a Novel Substrate and Inhibitor of Catechol O-Methyltransferase Modulates 4-Hydroxyestradiol-Induced Cyto- and Genotoxicity in MCF-7 Cells." Molecules 26, no. 7 (April 3, 2021): 2060. http://dx.doi.org/10.3390/molecules26072060.

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Nordihydroguaiaretic acid (NDGA) is a major lignan metabolite found in Larrea spp., which are widely used in South America to treat various diseases. In breast tissue, estradiol is metabolized to the catechol estrogens such as 4-hydroxyestradiol (4-OHE2), which have been proposed to be cancer initiators potentially involved in mammary carcinogenesis. Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens to their less toxic methoxy derivatives, such as 4-O-methylestradiol (4-MeOE2). The present study investigated the novel biological activities of NDGA in relation to COMT and the effects of COMT inhibition by NDGA on 4-OHE2-induced cyto- and genotoxicity in MCF-7 human breast cancer cells. Two methoxylated metabolites of NDGA, 3-O-methylNDGA (3-MNDGA) and 4-O-methyl NDGA (4-MNDGA), were identified in the reaction mixture containing human recombinant COMT, NDGA, and cofactors. Km values for the COMT-catalyzed metabolism of NDGA were 2.6 µM and 2.2 µM for 3-MNDGA and 4-MNDGA, respectively. The COMT-catalyzed methylation of 4-OHE2 was inhibited by NDGA at an IC50 of 22.4 µM in a mixed-type mode of inhibition by double reciprocal plot analysis. Molecular docking studies predicted that NDGA would adopt a stable conformation at the COMT active site, mainly owing to the hydrogen bond network. NDGA is likely both a substrate for and an inhibitor of COMT. Comet and apurinic/apyrimidinic site quantitation assays, cell death, and apoptosis in MCF-7 cells showed that NDGA decreased COMT-mediated formation of 4-MeOE2 and increased 4-OHE2-induced DNA damage and cytotoxicity. Thus, NDGA has the potential to reduce COMT activity in mammary tissues and prevent the inactivation of mutagenic estradiol metabolites, thereby increasing catechol estrogen-induced genotoxicities.
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de Castro-Catala, Marta, Neus Barrantes-Vidal, Tamara Sheinbaum, Artal Moreno-Fortuny, Thomas R. Kwapil, and Araceli Rosa. "COMT-by-Sex Interaction Effect on Psychosis Proneness." BioMed Research International 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/829237.

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Schizotypy phenotypes in the general population share etiopathogenic mechanisms and risk factors with schizophrenia, supporting the notion of psychosis as a continuum ranging from nonclinical to clinical deviance. Catechol-O-methyltransferase (COMT) is a candidate susceptibility gene for schizophrenia that is involved in the regulation of dopamine in the prefrontal cortex. Several recent studies have reported a sex difference in the impact of COMT genotype on psychiatric and cognitive phenotypes and personality traits. The present study investigated the association of COMT Val158Met (rs4680) with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults. The main finding was that sex moderates the association of COMT genotype with the negative dimension of both schizotypy and psychotic experiences. Male subjects carrying the Val allele tended to score higher on the negative dimension of both trait and symptom-like measures. The results from the present study are consistent with recent work suggesting an association between negative schizotypy and diminished prefrontal dopamine availability. They support the idea that a biological differentiation underlies the positive and negative schizotypy dimensions. Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.
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Mir, Rashid, Musadiq Bhat, Jamsheed Javid, Chandan Jha, Alpana Saxena, and Shaheen Banu. "Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease." Journal of Cardiovascular Development and Disease 5, no. 3 (July 13, 2018): 38. http://dx.doi.org/10.3390/jcdd5030038.

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Purpose: Catechol-O-methyltransferase (COMT) plays a central role in DNA repair and estrogen-induced carcinogenesis. The nonsynonymous single nucleotide polymorphism (SNP) in exon 4 G > A or Val108 > 158Met or rs4680 G > A influences COMT enzyme activity. The three phenotypes of the COMT enzyme activities include COMT A/A with low enzyme activity, COMT A/G with medium enzyme activity and COMT G/G with high enzyme activity. The Met allele is associated with low enzymatic activity resulting in higher levels of prefrontal dopamine. Conversely, the Val allele is associated with high enzymatic activity and lower levels of prefrontal dopamine. The Met allele has been associated with several psychiatric disorders such as panic disorder. Many recent epidemiologic studies have investigated the association between the COMT Val158Met polymorphism and coronary artery diseases risk, but the results are inconclusive. Therefore our study was aimed to explore the association between COMT Val158Met polymorphism and the risk of coronary artery disease in India. Methology: This study was conducted on 100 clinically confirmed cases of coronary artery diseases and 100 healthy controls. COMT Val158Met genotyping was performed by allele-specific polymerase chain reaction (AS-PCR). Results: A significant correlation was observed in the COMT Val158Met genotype distribution between the coronary artery disease cases and healthy controls (p = 0.008). The frequencies of all three genotypes, GG, GA, AA, reported in the CAD patients were 10%, 70%, and 20%, and 30%, 60%, and 10% in the healthy controls respectively. An increased risk of coronary artery disease was observed in the codominant inheritance model for COMT-GA vs. GG genotype with an OR of 3.5, 95% CI (1.58–7.74) p = 0.002) and COMT-AA vs. GG genotype with an OR of 6.0 95% CI (2.11–17.3) p = 0.003). The higher risk of coronary artery disease was observed in the dominant inheritance model for COMT (GA + AA) vs. GG genotype (OR 3.85, 95% CI 1.76–8.4, p < 0.007), whereas a non-significant association was found in recessive model for COMT (GG + GA vs. AA) (OR = 2.01, 95% CI (0.86–4.7) p = 0.72). The results indicated that A allele significantly increased the risk of coronary artery disease compared to the G allele (OR = 1.8, 95% CI (1.20–2.67) p = 0.004). COMT Val158Met polymorphism leads to a 6.0, 3.5 and 1.8-fold increased risk of developing coronary artery disease in the Indian population and providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Conclusions: It is concluded that COMT-AA genotype and A allele are significantly associated with an increased susceptibility to coronary artery disease in Indian population. A larger sample size can be the key to progress in establishing the genetic co-relationship of COMT polymorphism and cardiovascular disease.
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Šanjug, Jadranka, Krunoslav Kuna, Marina Šprem Goldštajn, Lidija Fumić Dunkić, Andreja Carek, and Dubravka Negovetić Vranić. "Relationship between COMT Gene Polymorphism, Anxiety, and Pain Perception during Labour." Journal of Clinical Medicine 12, no. 19 (September 29, 2023): 6298. http://dx.doi.org/10.3390/jcm12196298.

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Background: The COMT gene polymorphism is associated with neurological and psychiatric disorders and pain perception. The present study investigates the existence of anxiety and pain perception in relation to the COMT (catechol-O-methyltransferase) gene polymorphism in labouring women (during “natural” childbirth) with or without inhaled analgesia. Methods: A total of 181 women who chose vaginal birth were enrolled in this study. To present the difference in pain perception, the parturients were divided into one group (n = 90) that chose labour analgesia with inhaled nitrous oxide (50% nitrous oxide and 50% oxygen) and one group (n = 91) without analgesia. The blood samples were taken during the pregnancy as a part of routine pregnancy controls in the hospital. The COMT gene polymorphism was detected with the PCR technique. The pain perception of parturients was self-evaluated two times according to the VAS (Visual Analogue Scale), and anxiety as a personality trait was determined with the STAI-T (State Trait Anxiety Inventory). Pain perception as well as anxiety were compared according to COMT genotypes. Results: In the 181 pregnant women, there were 40 women (22%) of wild homozygotes (GG) of COMT, 95 women (53%) of mutant heterozygotes (GA), and 46 women (25%) of mutant homozygotes (AA). A negative association of pain perception with the GA (mutant heterozygote) polymorphism of the COMT gene versus the wild-type (GG polymorphism) was observed. The GA polymorphism of the COMT gene was associated with 0.46 units lower pain perception compared to the wild type (GG). The anxiety trait score in group AA was lower than in groups GA and GG. The difference reached statistical significance only when comparing AA versus GA (p > 0.042). Analgesic efficacy of nitrous oxide was noticed in 22% of labouring women who reported moderate pain (VAS score 4–7). Conclusions: The COMT gene polymorphism was associated with pain perception and anxiety among parturients. The COMT gene polymorphism GA was associated with negative pain perception among labouring women. Nitrous oxide showed statistical significance in anxiolytic efficacy during labour in women with mild anxiety as a personality trait. Anxiolytic efficacy of nitrous oxide has shown better efficacy in parturients with the COMT gene polymorphism AA.
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Yang, Xiaolei, Jinghuan Zhang, and Shun Zhang. "No association of COMT with insight problem solving in Chinese college students." PeerJ 7 (April 15, 2019): e6755. http://dx.doi.org/10.7717/peerj.6755.

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Genes involved in dopamine (DA) neurotransmission, such as the catechol-O-methyltransferase gene (COMT), have been suggested as key genetic candidates that might underlie the genetic basis of insight. In a sample of Chinese college students, this study examined whether COMT was associated with individual differences in the ability to solve classic insight problems. The results demonstrated that COMT was not associated with insight problem solving and there was no gender-dependent effect. This study, together with previous studies, raises the possibility of a complex relationship between COMT and insight problem solving.
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Pacheco-Romero, José, Doris Huerta, Oscar Acosta, and Santiago Cabrera. "Polimorfismo en el gen COMT en una muestra de gestantes normales y con restricción del crecimiento intrauterino en un hospital de Lima." Anales de la Facultad de Medicina 74, no. 2 (May 31, 2013): 129. http://dx.doi.org/10.15381/anales.v74i2.2385.

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Antecedentes: Los procesos fisiopatológicos que ocurren a nivel celular y molecular en la restricción de crecimiento intrauterino (RCIU) son aún desconocidos. La catecol-O-metiltransferasa (COMT) es una enzima de fase II que inactiva los catecol estrógenos al transferir un grupo metílico. Se conoce un polimorfismo funcional Val158 Met en el gen COMT como un marcador susceptible para diversas enfermedades maternoperinatales, existiendo estudios que sugieren que el alelo que codifica una COMT de baja actividad puede ser un marcador susceptible para RCIU. Por lo tanto, el estudio del polimorfismo COMT ofrece una nueva estrategia para la evaluación de marcadores genéticos que pueden ser utilizados para la detección de ciertas alteraciones asociadas al embarazo. Objetivos: Establecer la asociación entre el polimorfismo Val158Met catecol-O-metiltransferasa (COMT) y la restricción de crecimiento intrauterino. Institución: Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Diseño: Estudio tipo relacional (asociativo), con diseño observacional, tipo caso-control (no experimental). Materiales: Muestra de sangre materna de parturientas. Métodos: Durante el año 2011, se obtuvo 81 muestras para genotipaje del gen COMT. De ellas, 26 (32,1%) correspondieron a parturientas con RCIU (casos) y 55 (67,9%) a muestras de madres de hijos sin RCIU (controles). La distribución de los genotipos fue evaluada usando la prueba de chi cuadrado. Se comprobó la distribución proporcional de los genotipos en los grupos con RCIU y sin RCIU con la hipótesis nula de Hardy-Weinberg. Las madres participantes firmaron un consentimiento informado. Principales medidas de resultados: Asociación entre los genotipos COMT y la RCIU, y entre los alelos COMT Val/Met y la RCIU. Resultados: Las distribuciones de los genotipos en los grupos con RCIU y sin RCIU estuvieron de acuerdo a la hipótesis nula de Hardy-Weinberg. Al relacionar los genotipos COMT Val/Met con la condición de RCIU, la prueba X2=1.8057, gl=2, p=0.4054, no encontró asociación entre dichos genotipos y la RCIU. Al determinar la asociación entre los alelos COMT y la RCIU, tampoco se encontró asociación entre los alelos COMT Val/Met y la condición de RCIU en la muestra estudiada, con prueba X2=0.3659, gl=1, p=0.5453. Conclusiones: No se encontró asociación entre los genotipos COMT y la RCIU, ni entre los alelos COMT Val/Met y la RCIU, en la muestra estudiada.
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Bramon, E., E. Dempster, S. Frangou, C. McDonald, P. Schoenberg, J. H. MacCabe, M. Walshe, P. Sham, D. Collier, and R. M. Murray. "Is there an association between the COMT gene and P300 endophenotypes?" European Psychiatry 21, no. 1 (January 2006): 70–73. http://dx.doi.org/10.1016/j.eurpsy.2005.11.001.

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AbstractP300 wave anomalies correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The COMT gene is thought to influence cognitive performance and to be a susceptibility gene for schizophrenia. Unlike two previous studies, we found no significant influence of the COMT gene on P300 amplitude or latency in 189 individuals examined. The well-supported role of the COMT gene both in dopamine catabolism as well as in prefrontal cognition makes a strong theoretical case for the influence of COMT Val158Met polymorphism on P300 endophenotypes. However, the available neurophysiologic evidence suggests that any such association, if present, must be very subtle.
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Moraes, Leopoldo Silva de, Marcelina Ribeiro da Silva, Lorena Araújo da Cunha, Simone Machado da Rocha, and Carlos Alberto Machado da Rocha. "Gene COMT e sua possível relação com a esquizofrenia." Genética na Escola 14, no. 1 (April 27, 2019): 78–85. http://dx.doi.org/10.55838/1980-3540.ge.2019.313.

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A esquizofrenia é um transtorno psiquiátrico grave e acomete pessoas de todas as classes sociais. Caracterizado por sintomas positivos como psicose, delírios e alucinações, e sintomas negativos como retraimento social e distanciamento afetivo, que são causados por diversos fatores biopsicossociais; fatores genéticos podem estar intimamente relacionados ao desenvolvimento desta doença. Neste artigo é abordada uma possível relação do gene COMT com o aparecimento de alterações cerebrais envolvidas no surgimento da esquizofrenia. O gene COMT localizase no braço longo do cromossomo 22, codifica a enzima COMT (catecol-O-metiltransferase) que está envolvida na via de degradação de neurotransmissores catecolaminérgicos como a dopamina. O artigo também mostra um polimorfismo funcional deste gene, que afeta a disponibilidade da enzima e, consequentemente, altera importantes vias dopaminérgicas. Uma hipótese interessante considera estas alterações como possíveis causas de esquizofrenia.
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Brooks, D. J. "Safety and tolerability of COMT inhibitors." Neurology 62, Issue 1, Supplement 1 (January 12, 2004): S39—S46. http://dx.doi.org/10.1212/wnl.62.1_suppl_1.s39.

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Kuhn, W., D. Woitalla, H. Russ, M. Gerlach, and Th Müller. "Potentielle Risiken zentral wirksamer COMT-Hemmer." Aktuelle Neurologie 25, S 4 (December 1998): S277—S278. http://dx.doi.org/10.1055/s-2007-1017744.

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Greenwood, Jessica, Huy Pham, and Jose Rey. "Opicapone: A third generation COMT inhibitor." Clinical Parkinsonism & Related Disorders 4 (2021): 100083. http://dx.doi.org/10.1016/j.prdoa.2020.100083.

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Grant, Jon E., Eric W. Leppink, Sarah A. Redden, Brian L. Odlaug, and Samuel R. Chamberlain. "COMT genotype, gambling activity, and cognition." Journal of Psychiatric Research 68 (September 2015): 371–76. http://dx.doi.org/10.1016/j.jpsychires.2015.04.029.

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Lee, C. T., and H. K. Lee. "COMT gene polymorphism in alcohol dependence." European Neuropsychopharmacology 12 (October 2002): 388. http://dx.doi.org/10.1016/s0924-977x(02)80640-x.

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Sand, P., P. Eichhammer, A. Putzhammer, M. Albus, D. Wildenauer, M. Borrmann-Hassenbach, S. Schwab, P. Dallinger, B. Langguth, and G. Hajak. "P.6.063 COMT haplotypes in schizophrenia." European Neuropsychopharmacology 13 (October 2003): S452. http://dx.doi.org/10.1016/s0924-977x(03)92361-3.

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Arboleya, Luis. "Polimorfismos del gen COMT y fibromialgia." Reumatología Clínica 3, no. 1 (January 2007): 48–49. http://dx.doi.org/10.1016/s1699-258x(07)73599-4.

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McCarthy, Jeanette J. "COMT and schizophrenia: biology meets genetics." Trends in Biotechnology 19, no. 8 (August 2001): 283–84. http://dx.doi.org/10.1016/s0167-7799(01)01747-4.

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Nissinen, Erkki. "Chemistry and biochemistry of COMT inhibitors." European Journal of Pharmaceutical Sciences 34, no. 1 (June 2008): S7—S8. http://dx.doi.org/10.1016/j.ejps.2008.02.017.

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Bramon, E., E. Dempster, S. Frangou, C. McDonald, P. Schoenberg, J. H. MacCabe, M. Walshe, P. Sham, D. Collier, and R. M. Murray. "¿Hay una asociación entre el gen de la COMT y los endofenotipos de la onda P300?" European psychiatry (Ed. Española) 13, no. 5 (June 2006): 244–48. http://dx.doi.org/10.1017/s1134066500005208.

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ResumenLas anomalías de la onda P300 correlacionan con el riesgo genético de esquizofrenia y constituyen un enfofenotipo plausible para la enfermedad. Se piensa que el gen de la COMT influye en la ejecución cognitiva y es un gen de susceptibilidad para la esquizofrenia. A diferencia de dos estudios anteriores, no encontramos influencia significativa del gen de la COMT en la amplitud o la latencia de la onda P300 en 189 individuos examinados. El papel bien respaldado del gen de la COMT tanto en el catabolismo de la dopamina como en la cognición prefrontal constituye un fuerte argumento teórico para la influencia del polimorfismo Val158Met de la COMT en los endofenotipos de la onda P300. Sin embargo, los datos neurofisiológicos disponibles indican que cualquier asociación de esta índole, si está presente, debe ser muy sutil.
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Суханов, А. В., С. Е. Семаев, and В. Н. Максимов. "Associations of separate working memory parameters with comt genotypes in Western Siberia." Nauchno-prakticheskii zhurnal «Medicinskaia genetika», no. 6() (June 28, 2019): 43–49. http://dx.doi.org/10.25557/2073-7998.2019.06.43-49.

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Цель. Изучить ассоциации отдельных параметров оперативной памяти с полиморфным локусом Val158Met (rs4680) гена COMT у лиц молодого возраста. Материалы и методы. 371 участник 25-44 лет отобран из популяционной выборки г. Новосибирска. Исследование включало 199 (53,6%) мужчин (36,54 ± 5,67 года) и 172 (46,4%) женщины (36,84 ± 5,75 года). Когнитивные функции оценивались стандартизованными для целей скрининга методами: запоминание 10-ти слов по методике А.Р. Лурия, корректурная проба Бурдона, методика исключения понятий (словесный вариант теста) с фиксацией времени её выполнения, а также тест на речевую активность (тест называния животных). Геномную ДНК выделяли из венозной крови методом фенол-хлороформной экстракции. Генотипирование полиморфного локуса Val158Met (rs4680) гена COMT выполняли методом ПЦР с ПДРФ. Результаты. Выявлены статистически значимые ассоциации (p<0,05) полиморфного локуса Val158Met (rs4680) гена COMT с количеством правильно названных за 1 минуту животных в тесте на речевую активность, со временем, которое затрачивалось на выполнение теста исключения понятий, а также с первым воспроизведением запомненных слов сразу же после предъявления 10-ти слов в тесте по Лурия. Кроме того, количество жалоб на забывчивость постоянно используемых обследуемым номеров телефонов при наличии одного или двух аллелей А было достоверно выше. Заключение. Аллель А полиморфного локуса Val158Met (rs4680) гена COMT, особенно в гомозиготном состоянии, ассоциирован с параметрами оперативной памяти у жителей Новосибирска. Ain: to evaluate the associations between working memory parameters and Val158Met (rs4680) polymorphism of the COMT gene in young adults. Methods: 371 young adults of both sexes 25-44 years old were recruited from population sample of Novosibirsk. The study included 199 (53,6%) men (average age was 36,54 ± 5,67 years) and 172 (46,4%) women (average age was 36,84 ± 5,75 years). Cognitive function were determined by standardized screening methods. Luria’s 10-words test, letter cancellation test (modified Bourdon’s test), and test of excluded of incorrect words (verbal version of the test) with fixing the time for its implementation, as well as animal naming test were used. Genomic DNA was isolated from venous blood by the phenol-chloroform extraction. Genotyping of the Val158Met polymorphism (rs4680) of the COMT gene was performed using PCR with RFLP. Results: Statistically significant associations (p < 0,05) between quantity of the animals who are correctly called in 1 minute, with time which was spent for exclution of incorrect words, as well as with the first reproduction of the words memorized immediately in Luria test and Val158Met (rs4680) polymorphism of the COMT gene in young adults were revealed. Moreover the quantity of the complaints about the forgetfulness of used phone numbers had significantly higher in the presence of one or two A alleles of the Val158Met polymorphism of the COMT gene. Conclusion: The allele A of the Val158Met (rs4680) polymorphism of the COMT gene, especially in the homozygous state, has a significant association with the working memory parameters of Novosibirsk residents.
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Krzizike, Daniel D., Margie L. Clapper, and Andrew J. Andrews. "Abstract 2345: Specificity of catechol-O-methyltransferase (COMT) for hydroxyestrogens favors 2-OHEs over 4-OHEs." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2345. http://dx.doi.org/10.1158/1538-7445.am2022-2345.

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Abstract The contribution of estrogen receptor-mediated signaling to cancer progression and metastasis has been well documented. However, much less attention has been given to the role of estrogen metabolism in carcinogenesis. Parent estrogens are metabolized to 2- and 4-hydroxyestrogens (2-OHEs and 4-OHEs) that can retain their estrogenic activity, form reactive quinones that cause DNA damage, or become inactivated primarily by the rate-limiting conjugation enzyme catechol-O-methyltransferase (COMT). The ability of 4-OHEs to induce genomic instability and the malignant transformation of human breast epithelial cells has been reported. Glucuronidation or sulfation of methylated hydroxyestrogens, produced by COMT, increases their solubility and facilitates their excretion via urine or feces. The extent to which catechol estrogens are methylated dictates, in part, their ability to initiate carcinogenesis verses protect against tumor formation. COMT is a ubiquitous polymorphic enzyme that is expressed in humans in both peripheral tissues (soluble, s-COMT) and the central nervous system (membrane-bound). The goal of the present study was to compare the rate at which human wild type (WT) s-COMT and its major polymorphic variant (V108M s-COMT) transfer the methyl group from S-adenosylmethionine to 2-OHE and 4-OHE. This was accomplished by expressing COMT in E. coli, followed by protein purification and steady state Michaelis-Menten kinetics. Production of methylated hydroxyestrogens (2-MeOEs and 4-MeOEs) was quantified using LC-MS/MS methodology. The resulting data indicate that WT s-COMT methylates catechol estrogens more efficiently than V108M s-COMT. In addition, the specificity constant (kcat/KM) of WT s-COMT for methylation of 4-OHE2 was 12-fold greater than that of V108M s-COMT. The kcat/KM of V108M s-COMT was 4-fold greater for 2-OHE2 vs. 4-OHE2. Based on the enhanced catalytic efficiency of WT s-COMT in converting 2-OHEs to 2-MeOEs, 4-OHEs may have greater potential to cause DNA damage. Additional studies are needed to determine if the V108M s-COMT variant contributes to increased risk for cancer. These data provide novel insight into the potential mechanism by which 4-OHEs promote hormone-induced carcinogenesis. This work was supported by an In Vino Vita Award from Fox Chase Cancer Center. Citation Format: Daniel D. Krzizike, Margie L. Clapper, Andrew J. Andrews. Specificity of catechol-O-methyltransferase (COMT) for hydroxyestrogens favors 2-OHEs over 4-OHEs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2345.
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Khalil, Heba, Susan M. Sereika, Feng Dai, Sheila Alexander, Yvette Conley, Gary Gruen, Li Meng, Peter Siska, Ivan Tarkin, and Richard Henker. "OPRM1 and COMT Gene–Gene Interaction Is Associated With Postoperative Pain and Opioid Consumption After Orthopedic Trauma." Biological Research For Nursing 19, no. 2 (November 30, 2016): 170–79. http://dx.doi.org/10.1177/1099800416680474.

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Background: mu-opioid receptor ( OPRM1) and catechol-O-methyltransferase ( COMT) contribute to the neurotransmission pathway of pain. COMT affects mu receptor expression and density in the brain. The aim of this study was to explore the OPRM1 and COMT interaction effects on postoperative pain and opioid consumption. Methods: This cross-sectional exploratory study used genotype and clinical data from 153 postoperative patients. Using multiple regression analyses, four single-nucleotide polymorphisms of COMT (rs6269, rs4633, rs4818, and rs4680), their haplotypes, and diplotypes were considered for their interactions with A118G of OPRM1 regarding postoperative pain and opioid consumption. Results: For opioid consumption, significant interactions were found between OPRM1 A118G and COMT rs4680 ( p = .037) and between OPRM1 and COMT rs4633 ( p = .037). Patients having Met158Met of COMT rs4680 and AG/GG of OPRM1 or TT of COMT rs4633 and AG/GG of OPRM1 consumed the largest amount of opioid compared to those having other combinations. For postoperative pain, a significant interaction was found between OPRM1 and the low pain sensitivity (LPS; GCGG) haplotype of COMT ( p = .017). For patients with no copies of the LPS haplotype, AA of OPRM1 A118G was significantly associated with higher pain scores compared to the variant AG/GG. However, the opposite direction was observed for patients with at least one copy of the LPS haplotype. Conclusions: The interaction of OPRM1 with COMT may contribute to variability in postoperative pain and opioid consumption. Additional larger studies are needed to confirm findings.
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Gong, L., C. He, Y. Yin, Q. Ye, F. Bai, Y. Yuan, H. Zhang, et al. "Nonlinear modulation of interacting between COMT and depression on brain function." European Psychiatry 45 (September 2017): 6–13. http://dx.doi.org/10.1016/j.eurpsy.2017.05.024.

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AbstractBackground:The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.Methods:Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.Results:We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).Conclusion:Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.
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STEFANIS, NICHOLAS C., CÉCILE HENQUET, DIMITRIOS AVRAMOPOULOS, NIKOLAOS SMYRNIS, IOANNIS EVDOKIMIDIS, INEZ MYIN-GERMEYS, COSTAS N. STEFANIS, and JIM VAN OS. "COMT Val158Met moderation of stress-induced psychosis." Psychological Medicine 37, no. 11 (July 20, 2007): 1651–56. http://dx.doi.org/10.1017/s0033291707001080.

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ABSTRACTBackgroundExposure to stressful life events increases the risk of developing a psychotic disorder. Moreover, increased reactivity to stress seems to represent part of the vulnerability for psychosis. This study aimed to investigate whether a functional polymorphism in the catechol-O-methyltransferase (COMT Val158Met) gene moderates the psychosis-inducing effects of stress.MethodA semi-experimental stress exposure paradigm was used in a sample of 306 genotyped young men (aged 19–24 years), in whom measures of psychotic symptoms were obtained at recruitment in the Greek army (exposed condition) and again after 18 months of military training (unexposed condition).ResultsStress exposure at army induction was associated with an increased level of psychotic symptoms. In addition, carriers of the COMT Val158Met Val allele were more susceptible to the effect of stress on the psychosis outcome than those with the Met/Met genotype (test for interaction: χ2=5·02, df=1, p=0·025).ConclusionThe COMT Val158Met genotype may moderate the effect of stress on psychotic symptoms.
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Yadav, Sharawan, Naveen Kumar Singhal, Virendra Singh, Neeraj Rastogi, Pramod Kumar Srivastava, and Mahendra Pratap Singh. "Association of Single Nucleotide Polymorphisms in CYP1B1 and COMT Genes with Breast Cancer Susceptibility in Indian Women." Disease Markers 27, no. 5 (2009): 203–10. http://dx.doi.org/10.1155/2009/346497.

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Cytochrome P450 1B1 (CYP1B1) and catechol-$O$-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of COMT. The present study was performed to evaluate the associations of CYP1B1 Leu432Val and/or COMT Val158Met polymorphisms with total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit statistically significant association with breast cancer risks when analyzed individually, COMT wild type (Val158Val) in combination with CYP1B1 heterozygous variant (Leu432Val) [OR: 0.21; 95% CI (0.05–0.82), p value; 0.021] and COMT heterozygous variant (Val158Met) in combination with CYP1B1 wild type (Leu432Leu) [OR: 0.29; 95% CI (0.08–0.96), p value; 0.042] showed significant protective association with premenopausal breast cancer risk. The results demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their inverse combination offer protection against breast cancer in premenopausal Indian women.
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Männistö, Pekka T., and Seppo Kaakkola. "Catechol-O-methyltransferase (COMT): Biochemistry, Molecular Biology, Pharmacology, and Clinical Efficacy of the New Selective COMT Inhibitors." Pharmacological Reviews 51, no. 4 (December 1999): 593–628. https://doi.org/10.1016/s0031-6997(24)01423-6.

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Giakoumaki, Stella G., Panos Roussos, and Panos Bitsios. "Improvement of Prepulse Inhibition and Executive Function by the COMT Inhibitor Tolcapone Depends on COMT Val158Met Polymorphism." Neuropsychopharmacology 33, no. 13 (June 4, 2008): 3058–68. http://dx.doi.org/10.1038/npp.2008.82.

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Lipska, Barbara K., Shruti Mitkus, Mark Caruso, Thomas M. Hyde, Jingshan Chen, Radhakrishna Vakkalanka, Richard E. Straub, Daniel R. Weinberger, and Joel E. Kleinman. "RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met genotype and COMT enzyme activity." Human Molecular Genetics 15, no. 18 (August 11, 2006): 2804–12. http://dx.doi.org/10.1093/hmg/ddl222.

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