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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: This is the first report of an association between the COMT polymorphism and EPS susceptibility, and it is of interest in view of the increased use of antipsychotic drugs in bipolar patients in both the acute manic and the depressive phase.
Abstract: Objective The relationship is examined of the dopamine D2 receptor (DRD2) polymorphism (TaqIA, TaqIB, − 141 C Ins/Del) and the catechol- O -methyltransferase (COMT) polymorphism (A-278G, G158A) to the risk of antipsychotic-induced extrapyramidal symptoms (EPS) in schizophrenia and bipolar disorders. Participants comprised 80 cases presenting with EPS (Simpson-Angus Scale score > 3) and 188 controls presenting without EPS (Simpson-Angus Scale score ≤ 3) participated in this study. The COMT L allele conferred a reduction of EPS risk of 60% to heterozygotes, but the finding did not survive correction for multiple comparisons. In the bipolar subgroup, with a COMT L allele protection of 70%, the reduction remained significant after Bonferroni correction. The analysis of the COMT haplotypes revealed an association of the A–G haplotype with EPS risk in the overall group and the bipolar disorder subgroup, and an association of the A–A haplotype with EPS protection in the bipolar subgroup. No significant associations were found for DRD2 or COMT A-278G polymorphisms. This is the first report of an association between the COMT polymorphism and EPS susceptibility. These results are of interest in view of the increased use of antipsychotic drugs in bipolar patients in both the acute manic and the depressive phase.

45 citations

Journal ArticleDOI
TL;DR: The Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the age at onset (AAO) in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD.
Abstract: The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD). The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1±13.9, p=0.03) than the Val/Met (57.4±13.9) and the Met/Met genotypes (58.3±13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD.

45 citations

Journal ArticleDOI
TL;DR: The Met158 allele of the COMT gene confers a significantly increased risk for aggressive and violent behavior in schizophrenia, and may provide basis for developing informative strategies for reducing violence in patients with schizophrenia.

45 citations

Journal ArticleDOI
TL;DR: This is the first study to suggest that known and newly described polymorphisms in genes associated with executive and memory functions in healthy individuals and other clinical populations may modulate cognitive outcome in patients with brain tumors.
Abstract: BACKGROUND Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in the catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF), and dystrobrevin-binding protein 1 (DTNBP1) genes with cognitive functions and neuroimaging outcomes in patients with brain tumors. METHODS One hundred and fifty patients with brain tumors completed neuropsychological tests of attention, executive functions, and memory and were genotyped for polymorphisms in the COMT, BDNF, and DTNBP1 genes. Ratings of white matter (WM) abnormalities on magnetic resonance imaging scans were performed. RESULTS Multivariate regression shrinkage analyses, adjusted for age, education, treatment type, time since treatment completion, and tumor location, indicated a significant association between the COMT SNP rs4680 (Val158Met) and memory with lower scores in delayed recall (P < .01) among homozygotes (valine/valine). Additional COMT, BDNF and DTNBP1 SNPs were significantly associated with attention, executive functions, and memory scores. CONCLUSION This is the first study to suggest that known and newly described polymorphisms in genes associated with executive and memory functions in healthy individuals and other clinical populations may modulate cognitive outcome in patients with brain tumors.

44 citations

Journal ArticleDOI
TL;DR: An involvement of altered dopaminergic and/or noradrenergic neurotransmission as well as an interactive effect of COMT and 5‐HTTLPR gene variants in the etiology of BPD are suggested and underline the usefulness of analyses of gene–gene effects in diseases of complex inheritance with multiple genes involved.
Abstract: Borderline personality disorder (BPD) is characterized by a heterogeneous symptomatology with instability in impulse control, interpersonal relationships and self-image. BPD patients display repeated self-injury, chronic suicidal tendencies and emotional dysregulation, mainly dysregulation of negative affect. In its etiology, genetic and environmental factors have been suggested. Recently, an investigation in male healthy volunteers found gene–gene effects of the catechol-O-methyl-transferase (COMT) low-activity (Met158) and the low-expression allele of the deletion/insertion (short/long or S/L, respectively) polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR) on the central processing of aversive stimuli. The purpose of the present study was to test for association between BPD and the COMT Val158Met single nucleotide polymorphism (SNP), the 5-HTTLPR S/L variant and the interaction of these two gene variants. One hundred sixty one well-defined Caucasian BPD patients and 156 healthy controls were recruited from central Germany. In BPD patients, the genotype COMT Met158Met was over-represented compared to healthy controls (P = 0.0085; adjusted P = 0.034). We observed no differences in 5-HTTLPR genotypes between BPD and controls (P = 0.286). Additionally, the COMT Met158Met genotype was significantly over-represented in BPD patients carrying at least one 5-HTTLPR S allele (P = 0.0007; adjusted P = 0.028). Logistic regression analysis confirmed an interaction of the COMT Met158 and the 5-HTTLPR S allele (P = 0.001). These data suggest an involvement of altered dopaminergic and/or noradrenergic neurotransmission as well as an interactive effect of COMT and 5-HTTLPR gene variants in the etiology of BPD, and underline the usefulness of analyses of gene–gene effects in diseases of complex inheritance with multiple genes involved. © 2008 Wiley-Liss, Inc.

44 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202338
202265
202129
202032
201931
201834