Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “COMT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed2002

[Association study of heroin-dependence and -287 A/G polymorphism of catechol-O-methyltransferase gene].

OBJECTIVE: To detect the relationship between heroin-dependence and -287 A/G polymorphism of catechol-O-methyltransferase(COMT) gene. METHODS: Genotype and allele frequencies of -287 A/G polymorphism of COMT gene were examined in 268 heroin-dependent subjects and 177 normal controls. RESULTS: Weak but significant difference in genotype of -287 A/G polymorphism of COMT gene was observed between heroin-dependent subjects and controls (chi(2)=7.41, P=0.025), and genotype AA was higher in the former. The frequency of allele A of -287 A/G polymorphism of COMT gene was also significantly higher in heroin-dependent subjects than in the controls (chi(2)=5.69, P=0.017). CONCLUSION: The results suggested that liability to heroin-dependence was associated with -287 A/G polymorphism of COMT gene.

Adolescent↗
PubMed2003

Catechol-O-methyltransferase genotype and dopamine regulation in the human brain.

A functional polymorphism in the gene for catechol-O-methyltransferase (COMT) has been shown to affect executive cognition and the physiology of the prefrontal cortex in humans, probably by affecting prefrontal dopamine signaling. The COMT valine allele, associated with relatively poor prefrontal function, is also a gene that may increase risk for schizophrenia. Although poor performance on executive cognitive tasks and abnormal prefrontal function are characteristics of schizophrenia, so is psychosis, which has been related to excessive presynaptic dopamine activity in the striatum. Studies in animals have shown that diminished prefrontal dopamine neurotransmission leads to upregulation of striatal dopamine activity. We measured tyrosine hydroxylase (TH) mRNA in mesencephalic dopamine neurons in human brain and found that the COMT valine allele is also associated with increased TH gene expression, especially in neuronal populations that project to the striatum. This indicates that COMT genotype is a heritable aspect of dopamine regulation and it further explicates the mechanism by which the COMT valine allele increases susceptibility for psychosis.

Adult↗
PubMed2003

[Association study of heroin dependence and catechol-O-methyltransferase gene].

OBJECTIVE: To detect the relationship between heroin dependence and catechol-O-methyltransferase (COMT) gene. METHODS: Genotype and allele frequencies of 108 val/met and 900 Ins C/Del C polymorphisms of COMT gene were examined in 313 heroin-dependent subjects and 214 normal controls. RESULTS: No differences in genotype and allele frequencies of 108 val/met polymorphism of COMT gene were observed between heroin-dependent subjects and normal controls (genotype-wise: chi-square=1.67, P=0.43; allele-wise: chi-square=1.23, P=0.27). No differences in genotype and allele frequencies of 900 Ins C/Del C polymorphism of COMT gene were observed between heroin-dependent subjects and normal controls (genotype-wise: chi-square=3.73, P=0.16; allele-wise: chi-square=0.76, P=0.38). CONCLUSION: The results suggested that neither 108 val/met polymorphism nor 900 Ins C/Del C polymorphism of COMT gene was associated with heroin dependence.

Adolescent↗
PubMed2004

[Association between catechol-methyltransferase gene polymorphism and pregnancy induced hypertension].

OBJECTIVE: The Catechol-o-methyltransferase (COMT) gene contains a common functional polymorphism at locus Val158/108Met. This study was to investigate the association between COMT gene polymorphism and pregnancy-induced hypertension (PIH). METHODS: One hundred and two pregnant women with PIH (PIH group) and 94 normal pregnant women (control group) matched for age and gestation were recruited. Participants were genotyped for COMT at the Val158/108Met locus using PCR-based restriction fragment length polymorphism (RFLP) method. RESULTS: The frequencies of COMT HH, HL and LL genotypes were 56.9%, 38.2% and 4.9% in PIH group, respectively. These were 47.9%, 43.6% and 8.5% in normal control group, respectively (P > 0.05). The frequencies of the two alleles H and L were 76.0% and 24.0% in PIH group, and 69.7% and 30.3% in control group, respectively (P > 0.05). CONCLUSION: The COMT G1947-->A gene polymorphism is not associated with the generation and the severity of PIH. The mutation genotype does not increase the risk of PIH.

Adult↗
PubMed2005

[A paired case-control study on related factors to attempted suicide].

OBJECTIVE: To understand the environmental risk factors on attempted suicide, and to study the interaction between factors as gene polymorphism of catechol-O-methyltransferase (COMT) associated to attempted suicide. METHODS: Paired case-control study of 205 suicide attempters (89 male, 116 female) and molecular biological techniques were used to study the relation between gene polymorphism of COMT, environmental factors and the rate of attempted suicide. Controls were paired with cases according to the same gender, similar age (no more than 3 years) and in the same district. RESULTS: There were no significant differences in gene types and gene frequency between case and control groups. Multivariate conditional logistic regression model analysis showed that COMT Val/Val 158/108, low education level, cigarette smoking, emotional conflicts, psychologic disorders and depression were risk factors of attempted suicide with OR values as 2.43 (95% CI: 1.10 - 5.40), 5.70 (95% CI: 1.88 - 17.27), 3.54 (95% CI: 1.02 - 12.36), 10.96 (95% CI: 4.74 - 25.34), 6.35 (95% CI: 1.68 - 24.05) and 11.30 (95% CI: 4.58 - 27.89) respectively. There was no first level interaction between any two risk factors. CONCLUSION: The study supported that low education level, cigarette smoking, affective conflicts, psychiatric disorders, depression were risk factors of attempted suicide and COMT Val/Val 158/108 was suspected to be a susceptible gene type of attempted suicide but needs further study. The study also suggested that 116 bp in gene atlas be possibly correlated to high activity of COMT.

Adolescent↗
PubMed2005

No association between attention-deficit hyperactivity disorder and catechol-O-methyltransferase gene in Chinese.

Previous studies suggested that the catecholaminergic systems may be involved in the pathogenesis of attention-deficit hyperactivity disorder(ADHD). Since catechel-O-methyltransferase (COMT) is an enzyme involved in the degradation of catecholaminergic neurotransmitters of the dopaminergic and noradrenergic systems,it is possible that COMT may play a role in ADHD. To test this hypothesis, we used two family-based analyses,the transmission disequilibrium test (TDT) and the haplotype-based haplotype relative risk (HHRR), to examine the possible association between COMT gene and DSM-IV-diagnosed ADHD in a Chinese sample consisting of 79 ADHD probands and their parents. Both TDT (chi2 = 1.03, df=1, P > 0.05) and HHRR (chi2 = 1.08, df = 1, P > 0.05) analyses failed to detect preferential transmission of a COMT allele to the ADHD children. Our data suggested that there was no association between ADHD and the COMT gene in the Chinese population.

Alleles↗
PubMed1981

Changes in hypothalamic catechol-O-methyl-transferase during sexual differentiation of the brain.

1. An assay using [14C-methyl]-S-adenosyl-L-methionine was used to measure catecholamine-O-methyl-transferase (COMT) activity in the hypothalamus of newborn male and female rats from day 1 to day 12 and in adult animals after day 60. 2. There was no difference in COMT activity between sexes until day 8, when it became significantly higher in females. 3. Administration of 200 micrograms testosterone propionate to female rats at birth reduced the hypothalamic COMT level of the adult to that observed for male littermates. The response was dose-dependent in the range 50 to 200 micrograms. The hypothalamic content of COMT after puberty of male rats castrated at birth was comparable to that of post-pubertal females. 4. These results show that COMT, one of the enzymes involved in the control of brain biogenic amines, is also affected by the process of sexual differentiation of the brain.

Animals↗
PubMedDate not supplied

Role of a non-ionic detergent upon maintenance and radioisotopic determination of enzymes catechol-O-methyltransferase and monoamine oxidase in brain and adrenal tissues.

1. The effect of different concentrations of Triton-X-100, used as homogenization media for enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), was investigated. 2. Brain and adrenal COMT showed significant activation when treated with 0.2% Triton-X-100. 3. The activity of MAO in the brain and adrenal tissue was markedly inhibited by Triton-X-100 and the concentration required to provoke the inhibition was found to be much lower than that required to activate COMT. 4. When the tissues were kept in KCl-Triton-X-100 (0.9%-0.2%) for longer periods to study time related responses, brain COMT showed progressive increases in activity up to 4 hours of treatment and the increase persisted till 24 hours. Similar treatment of MAO enzyme preparation with Triton-X-100 induced strong inhibition of the enzyme activity (60% at 5 minutes and 55% at 24 hours). 5. The results suggest that the use of Triton-X-100 should be considered with extra care for determination of catecholamine regulating enzymes. It can activate one enzyme system whereas inhibit the other one. Therefore, different homogenization medias are required for the assay of enzymes of metabolism (MAO and COMT) and synthesis (tyrosine hydroxylase, phenylethano-l-amine-N-methyltransferase and dopamine beta hydroxylase).

Adrenal Glands↗
PubMed1993

Differences in subcellular distribution of catechol-O-methyltransferase and tyrosinase in malignant melanoma.

The activities of catechol-O-methyltransferase (COMT) and tyrosinase were measured in subcellular fractions obtained from transplantable melanotic and amelanotic hamster melanoma. The results showed that there was a substantial difference between the localization of these enzymes. Whereas tyrosinase was localized mainly in the large granule fraction, the highest COMT activity was found to be in fractions abundant in microsomal structures. As expected, subcellular fractions obtained from amelanotic melanoma contained low or undetectable tyrosinase activity. On the other hand, the same fractions exhibited higher COMT activity than those from the pigmented tumor. Relatively low specific activity of COMT in fractions containing coated vesicles does not support the idea that this enzyme could be responsible for the inhibition of melanin polymerization in these structures. Because melanogenic intermediates, such as 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid, are compartmentalized within membraneous structures, the preferential localization of COMT in cytosol and cytosolic membrane network might be advantageous for a detoxification role in (melanotic) melanocytes that produce dihydroxyindoles.

Animals↗
PubMed1976

Electrophoretic pattern of red blood cell catechol-o-methyltransferase in schizophrenia and manic-depressive illness.

Human red blood cell (RBC) catechol-O-methyltransferase (COMT) was analyzed by polyacrylamide gel electrophoresis (PAGE). One major enzyme band (B) is observed after electrophoresis. In addition, a minor band (A) of COMT activity comprising no more than 25% of the total activity, is also detectable. The rate of migration during electrophoresis of both bands of RBC COMT was the same in manic depressive, schizophrenic, and normal individuals. These results did not reveal genetic variations in the COMT molecule among these three groups. Furthermore, when total RBC COMT was measured there were no statistically significant differences between schizophrenic, manic-depressive, and control individuals.

Bipolar Disorder↗
PubMed1998

Synaptic physiology and ultrastructure in comatose mutants define an in vivo role for NSF in neurotransmitter release.

N-Ethylmaleimide-sensitive fusion protein (NSF) is a cytosolic protein thought to play a key role in vesicular transport in all eukaryotic cells. Although NSF was proposed to function in the trafficking of synaptic vesicles responsible for neurotransmitter release, only recently have in vivo experiments begun to reveal a specific function for NSF in this process. Our previous work showed that mutations in a Drosophila NSF gene, dNSF1, are responsible for the temperature-sensitive paralytic phenotype in comatose (comt) mutants. In this study, we perform electrophysiological and ultrastructural analyses in three different comt alleles to investigate the function of dNSF1 at native synapses in vivo. Electrophysiological analysis of postsynaptic potentials and currents at adult neuromuscular synapses revealed that in the absence of repetitive stimulation, comt synapses exhibit wild-type neurotransmitter release at restrictive (paralytic) temperatures. In contrast, repetitive stimulation at restrictive temperatures revealed a progressive, activity-dependent reduction in neurotransmitter release in comt but not in wild type. These results indicate that dNSF1 does not participate directly in the fusion of vesicles with the target membrane but rather functions in maintaining the pool of readily releasable vesicles competent for fast calcium-triggered fusion. To define dNSF1 function further, we used transmission electron microscopy to examine the distribution of vesicles within synaptic terminals, and observed a marked accumulation of docked vesicles at restrictive temperatures in comt. Together, the results reported here define a role for dNSF1 in the priming of docked synaptic vesicles for calcium-triggered fusion.

Animals↗
PubMed2003

Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia.

BACKGROUND: Cognitive dysfunction in the working memory domain seems to be under genetic control and is a candidate intermediate phenotype in schizophrenia. Genes that affect working memory processing may contribute to risk for schizophrenia. METHODS: Working memory and attentional processing were assessed in a large and unselected sample of schizophrenic patients, their healthy siblings, and controls (N = 250). We used the n-back task because it allows parametric analysis over increasing loads and delays and parsing of subcomponents of executive cognition and working memory, including temporal indexing and updating. Participants were genotyped for catechol-O-methyltransferase (COMT) at the Val158Met locus, which has been shown to affect executive cognition and frontal lobe function, likely because of genetically determined variation in prefrontal dopamine signaling. RESULTS: A significant COMT genotype effect was found: Val/Val individuals had the lowest n-back performance, and Met/Met individuals had the highest performance. Effects were similar in the 1- and 2-back conditions and across all groups, whereas no effect on the Continuous Performance Test was seen, suggesting that genotype was not affecting working memory subprocesses related to attention, load, or delay. Siblings also performed significantly worse than controls on the 1- and 2-back conditions. CONCLUSIONS: A prefrontal cognitive mechanism common to the 1- and 2-back conditions, probably executive processes involved in information updating and temporal indexing, is sensitive to the COMT genotype. Considering that the 3 participant groups were affected more or less linearly by the COMT genotype, an additive genetic model in which the effect of allele load is similar in its effects on prefrontally based working memory irrespective of the genetic or environmental background in which it is expressed is suggested. The findings also provide convergent evidence that an intermediate phenotype related to prefrontal cortical function represents a viable approach to understanding neuropsychiatric disorders with complex genetic etiologies and individual differences in cognition.

Adult↗
PubMed2005

Catechol O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder.

CONTEXT: Early-onset antisocial behavior accompanied by attention-deficit/hyperactivity disorder is a clinically severe variant of antisocial behavior that is associated with a particularly poor outcome. Identifying early predictors is thus important. Genetic and prenatal environmental risk factors and prefrontal cortical function are thought to contribute. Recent evidence suggests that prefrontal cortical function is influenced by a valine/methionine variant in the catechol O-methyltransferase (COMT) gene. OBJECTIVE: To test the a priori hypothesis that this genetic variant predicts early-onset antisocial behavior in a high-risk sample and further examine the effects of birth weight, an environmentally influenced index of prenatal adversity previously linked to childhood disruptive behaviors and genotype x birth weight interaction. DESIGN, SETTING, AND PARTICIPANTS: A family-based genetic study was undertaken between 1997 and 2003. Participants were prospectively recruited from child and adolescent psychiatry and child health clinics in the United Kingdom and included 240 clinic children who met diagnostic criteria for attention-deficit/hyperactivity disorder or hyperkinetic disorder. Participants underwent comprehensive standardized assessments including measures of antisocial behavior and IQ. Main Outcome Measure DSM-IV symptoms of childhood-onset conduct disorder rated by trained interviewers using a standard diagnostic interview. RESULTS: The results show main effects of the COMT gene variant (P = .002), birth weight (P = .002), and a significant gene x environment (COMT x birth weight) interaction (P = .006). CONCLUSIONS: Early-onset antisocial behavior in a high-risk clinical group is predicted by a specific COMT gene variant previously linked with prefrontal cortical function and birth weight, and those possessing the val/val genotype are more susceptible to the adverse effects of prenatal risk as indexed by lower birth weight.

Adolescent↗
PubMed2000

Pharmacogenetics of catechol-O-methyltransferase: frequency of low activity allele in a Ghanaian population.

Catechol-O-methyltransferase (COMT) catalyses the O-methylation of neurotransmitters, catechol hormones and drugs such as levodopa and methyldopa. Ethnic differences in COMT activity have been observed in several populations. Previous studies suggest that the g1947G>A low activity allele is less common in individuals of African origin. COMT genotyping was performed using a mini-sequencing method in 195 healthy Ghanaians with a frequency of the homozygous g1947G>A of 6%. This study provides confirmation that the low activity COMT allele is less common in individuals of African origin. This finding may be important clinically with regards to the treatment of many neuropsychiatric disorders and in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson's disease, depression and hypertension.

Adolescent↗
PubMed2004

Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels. REVIEWERS' CONCLUSIONS: In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.

Antiparkinson Agents↗
PubMed2003

Family-based and case-control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism.

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset behavioral disorder. Boys are more often affected than girls. Family, twin, and adoption studies have supported a strong genetic basis. Some studies show that a catechol-O-methyltransferase (COMT) polymorphism affecting enzyme activity was associated with personality characteristics and diseases, such as novelty-seeking personality, substance abuse, and heroin addiction, whose features are similar to ADHD or are associated with ADHD. These findings suggest that the COMT gene may be a candidate gene for ADHD. TDT, HHRR, and case-control association studies were conducted within a sample of 202 nuclear ADHD families, 340 ADHD cases, and 226 controls in the Han Chinese population. Diagnoses and ADHD subtypes were ascertained according to DSM-IV criteria using American Clinical Diagnostic Interviewing Scales. The HHRR analysis suggested that the low enzyme-activity COMT Met allele was preferentially transmitted to ADHD boys (160 trios, chi(2) = 3.858, P = 0.05, df = 1) but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity (50 trios, HHRR: chi(2) = 5.128, P = 0.024, df = 1; TDT: chi(2) = 4.558, P = 0.033, df = 1), especially the ADHD-I subtype (32 trios, HHRR: chi(2) = 5.792, P = 0.016, df = 1; TDT: chi(2) = 5.333, P = 0.021, df = 1). The case-control study revealed that the Val allele was more frequent in females meeting ICD-10 or DSM-IV criteria for ADHD than in female controls (86 and 79.5%, respectively, chi(2) = 4.059, P = 0.044, df = 1). Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions.

Adolescent↗
PubMed1989

Determination of catechol-O-methyltransferase activity in erythrocytes by high performance liquid chromatography with electrochemical detection.

A rapid assay employing HPLC with electrochemical detection for catechol-O-methyltransferase (COMT) activity in red blood cells is described. Enzyme activity is determined from erythrocyte lysates using S-adenosyl-L-methionine as methyl donor and 3,4-dihydroxybenzoic acid as substrate. The 3-O- and 4-O-methylated reaction products are measured by high-performance liquid chromatography with electrochemical detection. Human erythrocyte soluble form of COMT had Km values of 6.1 microM and 26.0 microM for S-adenosyl-L-methionine and dihydroxybenzoic acid, respectively. The mean O-methylation ratio for the soluble form of COMT was 5.3. An O-methylation ratio of 15.5 was estimated in the membrane fraction of an erythrocyte pool from three samples. The activities of soluble COMT in erythrocytes of some animal species are also reported. The procedure is easily automated, and a large number of samples can be processed during one working day.

Animals↗
PubMed1990

L-dopa as substrate for human duodenal catechol-O-methyltransferase and aromatic L-amino acid decarboxylase.

Catechol-O-methyltransferase (COMT) and aromatic L-amino acid decarboxylase (AADC) activities were determined in human gastrointestinal samples. L-dopa was used as the substrate and the reaction products 3-O-methyldopa (3OMD) and dopamine were separated by reversed phase HPLC and detected by electrochemical or UV detection. COMT activities varied between 40-350 pmol/mg/min and AADC activities between 100-3300 pmol/mg/min in different parts of the gastrointestinal tract. COMT inhibitors nitecapone (OR-462) and OR-611 effectively inhibited human gastrointestinal COMT activity in vitro, the IC50 values ranging from 10-20 nM and 5-75 nM, respectively. In vitro carbidopa inhibited AADC slightly more effectively than benserazide.

Aromatic-L-Amino-Acid Decarboxylases↗