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COMT Genotype (comt + genotype)
Selected AbstractsCatechol-O-methyltransferase val108/158met genotype and response to antipsychotic medication in schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2007Ari Illi Abstract Catechol-O-methyltransferase (COMT) gene has been investigated as a possible candidate gene in schizophrenia. The most studied polymorphism has been the functional val108/158met polymorphism of this COMT gene. There is also some evidence that this polymorphism could be related to drug response to antipsychotics in schizophrenia. COMT enzyme inactivates dopamine and noradrenaline. Based mainly on the original dopamine theory of schizophrenia, our primary hypothesis was that the maintenance dose of antipsychotics would be higher in patients with the low activity COMT genotype. In this study we evaluated the current daily dosage of antipsychotics in 180 patients with schizophrenia in connection with the COMT genotype. We could not demonstrate any clearly significant effect of this particular COMT genotype in relation to the daily maintenance dosages of antipsychotics in patients with schizophrenia. Copyright © 2007 John Wiley & Sons, Ltd. [source] Tissue histopathology, clinical chemistry and behaviour of adult comt -gene-disrupted miceJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2003Kristiina Haasio Abstract Catechol- O -methyltransferase (COMT) enzyme is a widely distributed enzyme that catalyses O -methylation of catecholamines and other compounds having a catechol structure. Because there has been some concern about the consequences of a low COMT activity in the development of oestrogen-dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of Comt -gene-disrupted mice were studied at the age of 12 months. Owing to the high COMT activities in liver and kidney and the role of COMT in the metabolism of catechol oestrogens, special emphasis was given to the histology of the liver, kidney and oestrogen-dependent organs such as mammary glands and uterus. The mice of both heterozygous and homozygous genotypes appear to be physically healthy and fertile. Diurnal motility rhythm and behaviour in measuring anxiety and depression were equal in all genotypes. At the age of 12 months, the body weight of homozygous mice was 7,9% lower than that of the other groups. This was re,ected in histology as a diminished incidence of vacuolation of liver cells (fatty change). Macroscopic pathology and histopathology revealed no abnormal ,ndings in any COMT genotype. The values of some clinical chemistry parameters, such as alkaline phosphatase, alanine aminotransferase, urea, glucose, calcium and proteins, were at a higher level in homozygous animals compared with the wild-type mice. However, all the values remained within the normal physiological range, and the differences in enzyme levels between genotypes were not re,ected as histopathological ,ndings in the relevant organs. No changes in haematological parameters or plasma catecholamine concentrations were noted but plasma 3,4-dihydroxyphenylethylene glycol levels were high in COMT null mice. The results suggest that the full or 50% lack of Comt gene as such is not associated with any toxic consequences. Copyright © 2003 John Wiley & Sons, Ltd. [source] The COMT val158met Polymorphism Is Associated With Peak BMD in Men,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2004Mattias Lorentzon Abstract The associations between the functional val158met polymorphism of the estrogen-degrading COMT enzyme and skeletal properties in young men were investigated. BMD was associated with COMT genotype. Introduction: Peak BMD is an important predictor of future risk of osteoporosis, and it is to a large extent determined by genetic factors. Estrogens are involved in the accretion of bone mass during puberty. Catechol- O -methyltransferase (COMT) is involved in the degradation of estrogens. There is a functional polymorphism in the COMT gene (val158met), resulting in a 60,75% difference in enzyme activity between the val (high activity [H]) and met (low activity [L]) variants. The aim of this cross-sectional study was to investigate the associations between this polymorphism and peak BMD in young men. Materials and Methods: A total of 458 healthy men (mean age, 19 ± 0.6 years) were genotyped and classified as COMTLL, COMTHL, or COMTHH. Areal BMD (aBMD) was measured by DXA. Cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. The associations between COMT genotype and skeletal phenotypes were determined. Results and Conclusions: Regression models using physical activity, height, weight, age, and COMT genotype as covariates showed that COMT genotype was an independent predictor of aBMD in the total body and in all femur locations investigated, but not in the spine. The values for COMTHL and COMTHH were very similar, and therefore, they were pooled into one group. aBMD at Ward's triangle, trochanter, and total femur were 4.9%, 4.5%, and 3.7% lower, respectively, in the COMTLL than in the COMTHL/HH group (p < 0.01). pQCT analyses showed that COMT genotype was an independent predictor of trabecular vBMD of the tibia, radius, and fibula. Trabecular vBMD of the radius and fibula in COMTLL was 5.3% and 7.4% lower, respectively, than that of the combined COMTHL/HH group. COMT genotype was associated with cortical vBMD but not with cortical cross-sectional area in the tibia. These findings show that the COMT polymorphism is associated with BMD in young adult men. [source] Association Between the Functional Polymorphism of Catechol- O -Methyltransferase Gene and Alcohol Consumption Among Social DrinkersALCOHOLISM, Issue 2 2000Jussi Kauhanen Background: A common functional genetic polymorphism in the catechol- O -methyltransferase (COMT) gene (Val158 Met) results in 3- to 4-fold differences in COMT enzyme activity and dopamine inactivation rate. Previous studies have shown that type I alcoholism is more common among subjects with low activity COMT genotype (LL), compared with high activity (HH) or heterozygotic (LH) genotypes. Methods: We studied alcohol consumption and the COMT genotype in middle-aged Finnish men (n= 896), who represented an unselected ethnically homogenous population sample and reported using alcohol during the past year. Average alcohol use in pure ethanol (grams per week) was compared between subjects with LL genotype and subjects with LH or HH genotypes. Results: Men with LL genotype (30% of all subjects) reported 27% higher weekly alcohol consumption compared with the two other genotype groups (p < 0.05). The difference remained statistically significant after a multivariate adjustment for sociodemographic factors and prior or existing diseases (p= 0.031). Conclusions: The results indicate that COMT polymorphism may contribute significantly to alcohol intake not only in alcoholics but also in a general male population. [source] Genetic polymorphism of catechol- O -methyltransferase and levodopa pharmacokinetic,pharmacodynamic pattern in patients with Parkinson's disease,MOVEMENT DISORDERS, Issue 6 2005Manuela Contin PharmD Abstract We explored the potential effect of catechol- O -methyltransferase (COMT) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a standard oral dose of levodopa in patients with Parkinson's disease (PD). We prospectively collected blood samples for COMT genotyping from a population of 104 PD patients. Each patient was examined by a standard oral levodopa/benserazide test, based on simultaneous serial measurements of plasma levodopa concentrations, finger-tapping motor effects and dyskinesia ratings, up to 4 hours after dosing. The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration, plasma elimination half-life, and the area under the plasma concentration,time curve. The main outcome levodopa pharmacodynamic variables were latency, duration, and magnitude of the motor effect elicited by the levodopa test dose, the area under the tapping effect,time curve, and the presence of dyskinesias. Nineteen patients (18%) harbored the low-activity homozygous COMT genotype (A/A), 63 patients (61%) carried the intermediate-activity heterozygous COMT genotype (A/G) and 22 patients (21%) had the high-activity homozygous COMT genotype (G/G). The three groups were comparable for vital and clinical characteristics. No significant difference was found in levodopa main pharmacokinetic,pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients. We failed to identify clinically relevant levodopa pharmacokinetic,pharmacodynamic response patterns associated with the COMT polymorphism in PD patients. © 2005 Movement Disorder Society [source] Stress-Induced Analgesia and Morphine Responses Are Changed in Catechol- O -methyltransferase-Deficient Male MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008Oleg Kambur It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level. [source] COMT genotypes and use of antipsychotic medication: linking population-based prescription database to the HUNT study,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Dr Knut Hagen Abstract Purpose The aim of this prospective study was to evaluate the impact of codon 158 polymorphism at the catechol- O -methyltransferase (COMT) gene on prescription of antipsychotic medication in a general population. Methods The sample comprised 2623 non-diabetic individuals who participated in the Nord-Trøndelag Health Study (HUNT) in the period 1995,97 and who were alive 1 January 2004. The subjects were followed up with respect to prescription of antipsychotic medication based on data obtained from the Norwegian prescription database. Results Among the group of 76 individuals who had been prescribed antipsychotic medication the distribution did not differ between genotypes and alleles when compared to a control group. For 47 individuals with at least three prescriptions a correlation between median total defined daily doses (DDDs) and genotype groups was found (Spearman's rho, ,0.40, p,=,0.01), being highest for the Met/Met genotype (250), intermediate for the Met/Val genotype (126) and lowest for the Val/Val genotype (47) (p,=,0.03). Conclusion In this population-based cohort of 2623 adults, the Val158Met polymorphism at the COMT gene had no major impact on number of individuals who had been prescribed antipsychotic medication. However, linkage to the prescription database may in an indirect way indicate an association between the COMT Val158Met polymorphism and treatment response or dose requirements of antipsychotic medication. Copyright © 2008 John Wiley & Sons, Ltd. [source] Increase in Free Choice Oral Ethanol Self-Administration in Catechol- O -Methyltransferase Gene-Disrupted Male MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008Anne Tammimäki Solutions containing ethanol or cocaine, or tap water were available ad libitum from drinking burettes for 4 weeks. Catechol- O -methyltransferase-deficient male mice consumed significantly more ethanol than their wild-type male littermates. In contrast, female mice did not show genotype differences in the consumption of ethanol solutions. During the cocaine experiment, male mice developed either a side preference or an aversion that obscured cocaine consumption. This pattern of drinking was not dependent on Comt genotype. In female mice, Comt genotype was not associated with cocaine consumption. In conclusion, disruption of Comt gene influenced ethanol consumption in a gender-dependent manner in mice, supporting the hypothesis that low catechol- O -methyltransferase activity is one of the predisposing factors for high alcohol consumption in males. [source] | ||||||||||