Topic
Catechol-O-methyl transferase
About: Catechol-O-methyl transferase is a research topic. Over the lifetime, 1646 publications have been published within this topic receiving 87360 citations.
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TL;DR: The localization of COMT in the leptomeninges, choroid plexus, and ciliary epithelium is consistent with a role for this enzyme in the separation of catechol compounds synthesized in the central nervous system, from those of peripheral origin.
52 citations
TL;DR: The use of cannabis could exert a modulator effect on the genotype, suppressing the delay effect for the age of onset in the case of the Met allele patients.
Abstract: New models of interaction between genetic and environmental factors have been proposed to explain the pathogenesis of schizophrenia. The Val158Met polymorphism of the COMT (Catechol-O-Methyltransferase) gene, involved in dopamine regulation and related to negative symptoms, has been previously thought to interact with cannabis use in the modulation of risk of psychosis. The aim of the study was to explore the existence of an interaction between COMT genotype and cannabis use in early stages of psychosis and its effects on the age of onset in a representative group of first-episode psychosis patients. Age of onset, DUP (Duration of Untreated Psychosis) and cannabis use (regular user versus sporadic or non-user) were assessed in 169 Caucasian patients with a first-episode schizophrenia spectrum disorder. COMT polymorphism was typed using PCR of the relevant region followed by digestion with NlaIII and electrophoresis. A multivariate ANCOVA was performed with DUP and age of onset as dependent variables, cannabis and the COMT genotype as fixed factors, and gender as a covariate. The MANCOVA was significant for age of onset and DUP. Cannabis users had a significant earlier age of onset. Age of onset was later in the Met homozygote group (non-significant). The cannabis-COMT interaction showed a significant effect on both DUP and age of onset. Post hoc analyses showed that differences between genotypes were only present in the non-users' group. Based on these results, the use of cannabis could exert a modulator effect on the genotype, suppressing the delay effect for the age of onset in the case of the Met allele patients.
52 citations
TL;DR: The possibility that combined COMT and MAO-A genotype is a significant factor in determining an individual's lifetime levodopa exposure warrants further investigation.
Abstract: Background: Clinical heterogeneity in the development of levodopa-induced dyskinesias (LID) suggests endogenous factors play a significant role in determining their overall prevalence. Objective: We hypothesised that single nucleotide polymorphisms (SNPs) in specific genes may result in a clinical phenotype conducive to an increased risk of LID. Methods: We examined the influence of SNPs in the catechol-O-methyltransferase (COMT), monoamine oxidase A (MAO-A) and brain-derived neurotrophic factor (BDNF) genes on LID in a cohort of 285 pathologically confirmed Parkinson's disease patients, using data from their complete disease course. Results: Dyskinetic patients demonstrated younger age at disease onset (60.3 vs. 66.4 years, p Conclusions: Individual SNPs in BDNF, COMT and MAO-A genes did not influence prevalence or time to onset of dyskinesias in this cohort. The possibility that combined COMT and MAO-A genotype is a significant factor in determining an individual's lifetime levodopa exposure warrants further investigation.
52 citations
TL;DR: There was a modest but statistically significant interaction between MAOA and COMT genotypes such that increased prefrontal catecholamine availability was associated with better working memory and suggest that assessment of multiple genes within functionally related systems may improve the understanding of the genetic basis of cognition.
Abstract: Individual differences in cognitive function are highly heritable and most likely driven by multiple genes of small effect. Well-characterized common functional polymorphisms in the genes MAOA, COMT, and 5HTTLPR each have predictable effects on the availability of the monoamine neurotransmitters dopamine, noradrenaline, and serotonin. We hypothesized that 5HTTLPR genotype would show little association with prefrontal cognitive performance, but that COMT and MAOA would have interacting effects on cognition through their shared influence on prefrontal catecholamine availability. We assessed the individual and epistatic effects of functional polymorphisms in COMT, MAOA, and 5HTTLPR on children's prefrontal cognitive function in nearly 6,000 children from the population-based Avon Longitudinal Study of Parents and Children (ALSPAC). Neither MAOA nor 5HTTLPR polymorphisms showed significant effects on cognitive function. In boys but not girls, there was a modest but statistically significant interaction between MAOA and COMT genotypes such that increased prefrontal catecholamine availability was associated with better working memory. These results suggest that assessment of multiple genes within functionally related systems may improve our understanding of the genetic basis of cognition. © 2010 Wiley-Liss, Inc.
52 citations
TL;DR: It is suggested that aging is accompanied by a decrease in liver and kidney COMT affinity for the substrate and a decreases in sensivity towards inhibition by tolcapone (evidenced by the increase in IC50 values).
Abstract: 1. The present work describes the catechol-O-methyltransferase (COMT) activities in the liver and kidney of developing and adult rats (aged 3, 6, 9, 18, 30 and 60 days; n = 5 per group) and evaluates the enzyme sensitivity to inhibition by tolcapone, a reversible COMT inhibitor. 2. COMT activity, evaluated by the ability to methylate adrenaline to metanephrine, was determined in liver and kidney homogenates prepared in 0.5 mM phosphate buffer (pH = 7.8) containing pargyline (0.1 mM), MgCl2 (0.1 mM), EGTA (1 mM) and S-adenosyl-L-methionine (0.1 mM). Vmax (in nmol mg-1 protein h-1) of liver COMT was found to decrease gradually with age, from 5.3 +/- 0.5 at the age of 3 days up to 2.9 +/- 0.2 at the age of 60 days; for the same age range, Km values (in microM; geometric means with 95% confidence limits) increased from 3.3 (1.0, 7.5) up to 13.1 (2.1, 24.1). At the age of 3 days, Vmax values for kidney COMT (2.6 +/- 0.1) were lower than those for the liver COMT. However, Vmax values for kidney COMT were found to increase up to 6.2 +/- 0.6 at the age of 18 days and then declined by 44% at the age of 30 and 60 days. In kidney, aging was also accompanied by an increase in Km values for COMT (from 2.7 [1.1, 4.3] up to 24.0 [11.7, 36.3]). 3. The sensitivity of liver and renal COMT activity to tolcapone was markedly dependent on the age, 3-days old rats being more sensitive to tolcapone than older animals. The IC50 values (in nM) for inhibition of liver COMT by tolcapone increased gradually with age, from 41 (26, 65) at the age of 3 days up to 720 (640, 800) at the age of 60 days. As was found in the liver, IC50 values (in nM) for inhibition of kidney COMT by tolcapone also increased with age, from 8 (6, 10) at the age of 3 days up to 177 (131, 240) at the age of 60 days. In all experimental groups, the IC50 values for inhibition of liver COMT by tolcapone was higher than those for kidney COMT. 4. In conclusion, these results suggest that aging is accompanied by a decrease in liver and kidney COMT affinity for the substrate (evidenced by the increase in Km values) and a decrease in sensitivity towards inhibition by tolcapone (evidenced by the increase in IC50 values). Furthermore, kidney COMT is shown to be more sensitive to inhibition by tolcapone than liver COMT, irrespective of the age of the animal.
52 citations