catechol-O-methyltransferase Val158Met Gene Polymorphism Research Articles

육상투척 선수군에서 ACTN3 유전자의 R577X 다형성과 COMT 유전자의 Val158Met 다형성의 분포

The aim of this study was to compare the genotype and allele distributions of the R577X(C1747T, rs1815739) polymorphism in α-actinin 3(ACTN3) gene and the Val158Met(G/A, rs4680) polymorphism in catechol-O-methyltransferase(COMT) gene between controls and athletes of throwing event in order to search for the useful genetic marker(s) influencing the athletic performance of throwing event. On the whole, seventy eight individuals were included in this study, and they grouped in controls(n=55) and throwers(n=23), respectively. Total genomic DNA was isolated from all subjects, and two genetic polymorphisms in each gene were assayed by SNaPshot method. In the case of the Val158Met polymorphism in COMT gene, there were no significant differences in genotype and allele distributions between controls and throwers, respectively. But, there were the significant differences in both genotype and allele frequencies of the R577X polymorphism in ACTN3 gene between two groups, respectively(p .05). Especially, the frequencies of RR genotype and R allele in this genetic polymorphism were overrepresented in throwers compared to controls, respectively. Thus, these results suggest that the R577X polymorphism in ACTN3 gene is likely to significantly influence the athletic performance of throwing event in at least Koreans. Because the genotype and allele frequencies of each genetic polymorphism can vary by ethnicity with different genetic bacjground, further studies by using other ethnic groups will be needed to replicate our positive association study result observed in the R577X polymorphism of ACTN3 gene.

COMTVal158Met polymorphism is associated with ecstasy (MDMA)-induced psychotic symptoms in the Turkish population.

Objectives:To investigate catechol-O-methyltransferase (COMT) Val158Met gene polymorphism in MDMA use disorder (MUD) by comparing genotype distributions between MUD patients and healthy controls considering clinical parameters.Methods:Eighty-two MUD patients’ were consecutively admitted to the outpatient psychiatry clinic in May 2019-January 2020, and 95 healthy volunteers were included in the case-control study. We used the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to determine COMT Val158Met polymorphism.Results:The COMT Val158Met genotype distribution and allele frequencies of the MUD patient group were significantly different from the healthy control group. The Met/Met genotype (OR: 2.692; 95% Cl: 1.272-5.698; p=0.008) and Met allele frequencies (OR: 1.716; 95% Cl: 1.118-2.633; p=0.013) were significantly higher in the control group than in MUD patients. When the COMT Val158Met genotype and allele frequency distributions were compared between 2 groups according to the psychotic symptoms in the MUD patient group, the COMT Val158Met genotype distributions were significantly different between the groups of patients. The percentage of patients with the Val/Val genotype was significantly lower in MUD patients with a psychotic symptom than the MUD patients without a psychotic symptom (OR: 2.625; 95% Cl: 1.069–6.446; p=0.033).Conclusion:The COMT Val158Met gene polymorphism was found to be related to the MUD-diagnosed Turkish patients and MDMA-induced psychotic symptoms.

Can COMT Val158Met Gene Polymorphism Predict Treatment Outcomes for Methylphenidates in ADHD Patients?

The COMT gene encodes for the Catechol-O-methyltransferase (COMT) enzyme, an enzyme responsible for the breakdown of dopamine and norepinephrine in the prefrontal cortical areas. The most common variation of the COMT gene is the Val158Met polymorphism (rs4680) which leads to a valine (Val) to methionine (Met) substitution at codon 158. It is plausible that variations in this gene may predict treatment outcomes to stimulants like methylphenidates used in the treatment of ADHD. The purpose of this study is to statistically evaluate this association to further the clinical implementation of personalized medicine. Quantitative data was collected from clinical trials where patients were genotyped for the COMT gene and were evaluated for treatment response to methylphenidates on a quantifiable scale. Correlational analysis (n=1094) showed a statistically significant association (p=0.003) between this genotype and treatment outcomes. The Odd’s ratio calculated from the binary outcomes (n=638 patients) depicted that the Val/Val carriers were 1.86 times more likely to respond positively to methylphenidate treatment compared to the Met allele carriers. Our analysis shows that variations in COMT gene can reliably predict treatment outcomes to Methylphenidates in ADHD patients. However, this association is based on the data extracted from 9 different clinical studies (n= 1094 patients). These studies had different sample sizes, ethnicities, and measurement scales which may have contributed to the heterogeneity in the overall sample data set, thereby diluting the power of the association. Nevertheless, this analysis adds to the body of pharmacogenomic evidence increasing the clinical utility of precision medicine.

Association study of Catechol-O-Methyltransferase (COMT) rs4680 Val158Met gene polymorphism and suicide attempt in Mexican adolescents with major depressive disorder

Aim We analyzed the association between SLC6A4, DRD2, COMT and MAOA genes and suicide attempt (SA) in Mexican adolescent patients with major depressive disorder (MDD). Methods The sample included 197 adolescents (127 females and 70 males) with principal diagnosis of MDD. Among them, 63 patients had SA at least once and 134 had not SA. The mean age of patients with and without SA was 15 ± 1.4 and 14 ± 1.5 years, respectively. We analyzed the genotype and allele distribution between patients with and without SA of SLC6A4 (5HTTLPR/rs25531), DRD2 (rs6275), COMT (rs4680), and MAOA (uVNTR). Results We did not find genotype or allele association between SA and SLC6A4 (χ2=0.67, p = 0.71; χ2=0.07, p = 0.77, respectively), DRD2 (χ2=0.05, p = 0.97; χ2=0.003, p = 0.95), and MAOA (females: χ2=0.86, p = 0.64; χ2=0, p = 1/males: χ2=0.008, p = 0.92) genes. However, there were differences in genotype frequencies of COMT/rs4680 between patients with SA and without SA (χ2=11.17, p = 0.003). Also, we observed a high frequency of Met158 allele showing an increased risk of having presented at least one SA (χ2=10.6, p = 0.001; OR = 1.43; 95% CI, 1.17–1.74). Conclusions Our findings showed an association between low activity genotype and allele of Val158Met polymorphism of COMT gene and SA in Mexican adolescents with MDD.

Brain predictive coding processes are associated to COMT gene Val158Met polymorphism

Predicting events in the ever-changing environment is a fundamental survival function intrinsic to the physiology of sensory systems, whose efficiency varies among the population. Even though it is established that a major source of such variations is genetic heritage, there are no studies tracking down auditory predicting processes to genetic mutations. Thus, we examined the neurophysiological responses to deviant stimuli recorded with magnetoencephalography (MEG) in 108 healthy participants carrying different variants of Val158Met single-nucleotide polymorphism (SNP) within the catechol-O-methyltransferase (COMT) gene, responsible for the majority of catecholamines degradation in the prefrontal cortex. Our results showed significant amplitude enhancement of prediction error responses originating from the inferior frontal gyrus, superior and middle temporal cortices in heterozygous genotype carriers (Val/Met) vs homozygous (Val/Val and Met/Met) carriers. Integrating neurophysiology and genetics, this study shows how the neural mechanisms underlying optimal deviant detection vary according to the gene-determined cathecolamine levels in the brain.

Investigation of Catechol-O-methyltransferase (COMT) gene Val158Met polymorphism in ovarian cancer

Objective:Catechol-O-methyltransferase (COMT), the product of the COMT gene, detoxifies the carcinogenic catechol estrogens. The aim of the present study was to examine the relationship between COMT Val158Met polymorphism and the risk of ovarian cancer.Material and Methods:The study groups consist of 94 individuals as a patients group with ovarian cancer (n=47) and control group (n=47). The allele and genotype frequencies were determined according to Hardy-Weinberg equilibrium (HWE). The allele and genotype frequencies. determined according to HWE. Genetic analysis were performed by real-time-polymerase chain reaction instrument, and the statistical analysis were performed by SPSS program.Results:Although no significant relationship was obtained among groups (p=0.413) regarding COMT gene Val158Met polymorphism, the genotype frequencies for COMT Val158Met (rs4860) polymorphism in groups was homozygote wild type GG genotype 25.5%, heterozygote GA genotype 46.8%, homozygote mutant AA genotype 27.7%.Conclusion:This study is the first to investigate the relationship between ovarian cancer and the Val158Met polymorphism in the COMT gene in a Turkish population. No statistically significant relationship was identified among genotypes belonging to the patient and control groups although sample sizes were relatively small and the analysis should be repeated in a larger cohort.

Catechol-O-methyltransferase gene Val158Met polymorphism and obsessive compulsive disorder susceptibility: a meta-analysis.

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that affects approximately 1-3% of the general population. It is characterized by disabling obsessions (intrusive unwanted thoughts) and/or compulsions (ritualized repetitive behaviors). Catechol-O-methyltransferase (COMT) enzyme has an important role in inactivation of dopamine and higher dopamine levels may be implicated in OCD, hence COMT gene is a suitable candidate for OCD. Several case-control studies have evaluated the role of COMT Val 158Met (rs4680;472G- > A) polymorphism as a risk factor for OCD but the results remained inconclusive, hence present meta-analysis was designed to find out correct assessment. All studies that investigated the association of COMT gene Val158Met polymorphism with OCD risk, were considered in the present meta-analysis. Statistical analysis was performed with the software program MetaAnalyst. In the current meta-analysis, 14 case-control studies with 1435 OCD cases and 2753 healthy controls were included. The results indicated significant association between COMT Val158Met polymorphism and OCD risk using allele contrast, homozygote and dominant models (ORA vs G = 1.14; 95% CI = 1.02-1.27; p = 0.01; ORAAvs.GG = 1.33; 95% CI = 1.09-1.62, p = 0.004; ORAA + AGvs.GG = 1.14; 95% CI = 1.0-1.32; p = 0.04). In subgroup analysis based on case gender, meta-analysis of male cases showed significant association using all five genetic models (ORAAvsGG = 1.99; 95%CI = 1.42-2.59; p = <0.001; ORAA + AGvs.GG = 1.59; 95% CI = 1.20-2.10; p = 0.001), but did not show any association between COMT Val 158Met polymorphism and OCD risk in females. In conclusion, results of present meta-analysis supports that the COMT Val158Met polymorphism is a risk factor for OCD especially for males.

The impacts of Val158Met in Catechol-O-methyltransferase (COMT) gene on moral permissibility and empathic concern

Dopamine levels in the brain influence emotional experiences and empathic responses to others' misfortune. Inspired by roles of Catechol-O-methyltransferase (COMT) in dopamine degradation and the link between moral judgment and empathic responses, this study investigated to what extent the Val158Met polymorphism of COMT gene contributes to individual differences in moral permissibility and empathic dispositions. One thousand two hundred and seventy-two Chinese Han college students, who were differentiated with the COMT Val158Met (rs4680) polymorphism, rated permissibility of harm in moral dilemmas and scored their empathic dispositions with Interpersonal Reactivity Index. The results showed a significant association between COMT Val158Met and the moral permissibility of committing harm. Individuals with the Val/Val genotype, which is associated with lower levels of dopamine, endorsed impersonal harm as more impermissible than those with the Val/Met and Met/Met genotypes. Results also showed that individuals with the Val/Val genotype showed higher empathic concern for others' misfortune. The findings provide the first evidence for the link between COMT gene and the moral permissibility, highlighting the roles of dopamine in social cognition.

Catechol-O-methyltransferase Val158Met polymorphism influences prefrontal executive function in early Parkinson's disease

ObjectiveThe catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinson's disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias. MethodsCognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions. ResultsThe COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women. ConclusionsOur results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication.

The Effect of Single Dose Methylphenidate on Neurometabolites according to COMT Gene Val158Met Polymorphism in the Patient with Attention Deficit Hyperactivity Disorder: A Study Using Magnetic Resonance Spectroscopy.

ObjectiveAttention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Thus, the present study aimed to determine the effects of a single dose of methylphenidate (Mph) on neurometabolite levels according to polymorphisms of the catechol-O-methyltransferase (COMT) gene.MethodsThis study evaluated the neurometabolite levels including N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) of ADHD patients, before and after treatment with Mph (10 mg) according to the presence of COMT polymorphisms. The spectra were obtained from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), cerebellum, and striatum.ResultsThe NAA levels of the val/val and val genotype carriers (val/val and val/met genotypes) increased in the DLPFC and ACC, respectively, following Mph treatment. The NAA/Cr ratio was lower in the DLPFC of val carriers than in the met/met genotype carriers prior to Mph administration. The Cho levels of the val/met genotype and val carriers increased in the striatum following Mph treatment. Following Mph treatment, the Cr levels of the met/met genotype carriers were higher than those of the val/met genotype and val carriers. Additionally, after Mph treatment, there was a significant increase in Cr levels in the DLPFC of the met/met genotype carriers but a significant decrease in such levels in the striatum of val/val genotype carriers.ConclusionThese findings suggest that polymorphisms of the COMT gene can account for individual differences in neuro-chemical responses to Mph among ADHD patients. Therefore, further studies are needed to fully characterize the effects of the Val158met polymorphism of the COMT gene on treatment outcomes in patients with ADHD.

Val158Met polymorphism of COMT gene and Parkinson's disease risk in Asians.

In previous study, we have found the catechol-O-methyltransferase (COMT) Val158Met polymorphism as an associated risk factor for Parkinson's disease (PD) in Asian rather than Caucasian populations. The aim of this study was to further evaluate the associations of PD risk with COMT polymorphisms in different Asian populations. We carried out a retrieval of studies that investigated associations between COMT Val158Met polymorphism and PD risk in Asians, and included the study if it met the eligibility criteria. Stata version 12.0 was used to analyze the data. A total of 13 studies including 1,834 patients and 2,298 controls were included. The overall result indicated that COMT Val158Met polymorphism was significantly associated with the risk of PD in Asians (AA vs others: OR=1.58, 95% CI 1.26-1.97, p<0.001; GG vs AA: OR=0.63, 95% CI 0.47-0.85, p=0.002; AA vs GA: OR=1.58, 95% CI 1.24-2.00, p<0.001). In Japanese population, the homozygote AA tends to increase the risk of PD (AA vs others: OR=1.54, 95% CI 1.10-2.15, p=0.012; AA vs GA: OR=1.61, 95% CI 1.14-2.29, p=0.008). This study showed that the Val158Met polymorphism of COMT gene may be associated with PD in Japanese rather than Chinese population. Further studies are needed to confirm this association in more ethnicities.

Clinical symptoms in fibromyalgia are associated to catechol-O-methyltransferase (COMT) gene Val158Met polymorphism

1. Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. The aim of this study was to explore the frequency and clinical significance of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism in a large cohort of Turkish patients with FMS.2. The study included 379 FMS patients and 290 controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses.3. The genotype frequencies of Val158Met polymorphism showed a small difference between FMS patients and healthy controls (p = 0.047), however, the Met/Met genotype was significantly higher in FMS patients than healthy controls (p = 0.016). No difference was observed for allele frequencies between two groups. Stratification analysis according to clinical features for this disease reveals that weight, FMS Impact Questionnaire score, algometry and Raynaud’s syndrome, were detected to have statistically significant associations with Val158Met polymorphism (p = 0.037, p = 0.042, p = 0.039 and p = 0.033, respectively). Pain sensitivity, measured by algometry, was statistically higher in patients with Met/Met genotype than the patients with Val/Val and Val/Met genotypes (p = 0.017).4. The results of this study suggested that COMT gene Val158Met polymorphism is positively associated with FMS and play a relevant role in the clinical symptoms of the disease.

Interaction between COMT Gene rs6267 Polymorphism and Maternal Parenting Behavior on Adolescents' Physical and Relational Aggression

The influencing factors and underlying mechanisms of aggressive behavior are important fundamental issues in research on human aggression. With the advancement of molecular genetics, the research on the mechanisms of aggression has reached molecular level in recent years. Recent studies using candidate gene strategy have demonstrated that the COMT(catechol-O-methyltransferase) gene was significantly associated with human aggression. However, existing research mainly focused on physical aggression, while the genetics mechanism of relational aggression has scarcely been investigated. To our knowledge, only two studies examined the genetic underpinnings of the two specific subtypes of aggression by examining the direct associations between COMT gene Val158 Met polymorphism and both physical and relational aggression, but these studies failed to investigate the gene-environment interaction. Recent research has revealed a new functionally single nucleotide polymorphism rs6267 in the COMT gene which also plays an important role in individual's development, but its possible interaction with environment on aggressive behavior remains unclear. The present study aimed to extend the previous research by examining the association between COMT gene rs6267 polymorphism and both physical and relational aggression among Chinese children and adolescents, with a particular focus on the possible moderating effects of maternal parenting behavior and gender on the association.One thousand two hundred and fifty eight children(male = 649) from 40 classes of 14 primary schools in Jinan City were followed from grade 4 till to grade 7. The subjects' physical and relational aggression were obtained through peer rating, and the maternal parenting behavior was measured by mother report. DNA was extracted from saliva. In detail, genotype at rs6267 polymorphism in the COMT gene was performed for each participant in real time with MassARRAY RT software version 3.0.0.4 and analyzed using the MassARRAY Typer software version 3.4(Sequenom). Pearson correlation and hierarchical regression analyses were conducted to examine the effect of rs6267 polymorphism and maternal parenting behavior on adolescent aggression. The main findings of the present study were as follows: Rs6267 polymorphism in the COMT gene significantly interacted with maternal parenting behavior in predicting adolescent physical aggression, but this interaction was observed only among males, such that maternal warmth negatively predicted male adolescent physical aggression among carriers of GG homozygote but not T allele. Similarly, maternal rejection and punishment only positively predicted male adolescent physical aggression among carriers of GG homozygote but not T allele. However, the interaction between rs6267 polymorphism in the COMT gene and maternal parenting behavior on adolescent relational aggression was not significant. The findings of the present study indicate that gene-environment interactions on adolescents' aggression may vary across physical and relational aggression and across gender, and thereby provide additional support for the dichotomy of these two subtypes of aggression. Besides, by elaborating the moderating effect of maternal parenting behavior and gender, the present study enriches the literature of the relation between COMT gene and aggression.

Catechol-O-methyltransferase Val158Met polymorphism and hyperactivity symptoms in Egyptian children with autism spectrum disorder

Catechol-O-methyltransferase (COMT) plays an important role in the catabolism of brain dopamine and norepinephrine, which have been implicated in the pathogenesis of Autism spectrum disorder (ASD) as well as in other neuropsychatric disorders. We aimed to investigate the association of COMT Val158Met gene polymorphism with ASD and to examine the influence of such genotypes on hyperactivity symptoms in ASD patients. Eighty ASD patients (mean age 9 ± 1.9 years) and 100 control children (mean age 8.9 ± 1.9 years) were examined. COMT Val58Met polymorphism was genotyped using Tetra-primer ARMS-PCR method. The clinical diagnosis of ASD and ADHD were confirmed according to the DSM-IV criteria for research. We found no significant difference in genotypes or alleles' frequencies of COMT Val158Met polymorphism between ASD patients and control group. There was a significant association between COMT (Val/Val) genotype and both increasing CARS (p=0.001) and hyperactivity scores (p=0.006). Regarding Conner's Score, the DSM-IV hyperactive impulsive were significantly higher in Val/Val genotype than both Met/Val and Met/Met genotypes (p=0.03). Our data suggested an association between COMT Val58Met polymorphism and hyperactivity symptoms in Egyptian children with ASD.

Catechol-O-methyltransferase Val158Met polymorphism and risk of autism spectrum disorders

Autism spectrum disorders (ASD) are a family of childhood-onset neurodevelopmental disorders with complex genetic mechanisms underlying their aetiology. The aim of this case-control study was to evaluate the effect of the catechol-O-methyltransferase (COMT) gene Val158Met polymorphism on ASD risk in a Chinese Han population. The COMT gene Val158Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in children (≤ 18 years old) with ASD and healthy control subjects. The frequency of the Val158/Val158 genotype in children with ASD (22/186; 11.8%) was significantly lower than in controls (38/186; 20.4%). When stratifying by select-item scores on the Autism Diagnostic Interview-Revised protocol, it was found that children with 'current overactivity' and 'ever overactivity' had a significantly lower frequency of the Val158/Val158 genotype than those without. There were no significant associations between the COMT gene Val158Met polymorphism and ASD subtypes. The COMT gene Val158Met polymorphism may be a biomarker for phenotypic variation in ASD, but these preliminary findings remain tentative, pending replication in larger, independent samples.

402 – An association study on children with gilles de la tourette’s syndrome and COMT gene polymorphism

Objective To investigate the association between catechol-O-methyl transferase (COMT) gene polymorphism and Gilles de la Tourette’s syndrome (GTS). Methods Using Amplification Refractory Mutation System(ARMS) PCR genotyping assay method, a polymorphism (val158met) of COMT gene was genotyped in 112 of all GTS patients including 54 GTS-alone patients, 48 GTS+ADHD patients among of them and 71 healthy controls. The correlation between positive association of polymorphism (val158met) of COMT gene in GTS and the age of onset in patients with GTS was also analyzed. Results When compared with healthy controls, genotype of val158met did not differ in total GTS patients or alone- GTS patients (x2=0.56, P = 0.756; x2= 1.05, P = 0.600 respectively). There is also no significant difference (P>0.05) in allele distribution of val158met in total GTS patients or alone- GTS patients when respectively compared with controls (x2= 0.18, P = 0.669; x2= 0.29, P = 0.593 respectively). However, Genotype distribution of val158met was significantly different between GTS+ADHD patients and controls (x2=6.35, P = 0.041). The frequency of the val allele of this locus was significantly higher in GTS+ADHD patients than those in controls (x2= 5.49, P = 0.019).The age of onset in children with GTS having the val/val genotype of COMT gene val158met polymorphism were significantly earlier than no val/val genotype (P = 0.016). Conclusion Polymorphism (val158met) of COMT gene may be associated with GTS children with comorbid ADHD, which may play an important role to make the age of onset in children with GTS become earlier.

An association study on Gilles de la Tourette's syndrome and catechol-O-methyl transferase gene polymorphism

Objective To investigate the association between catechol-O-methyl transferase (COMT) gene polymorphism and Gilles de la Tourette’s syndrome(GTS). Methods Using Amplification Refractory Mutation System(ARMS) PCR genotyping assay method, a polymorphism (val158met) of COMT gene was genotyped in 112 of all GTS patients (total GTS group) including 54 GTS-alone patients group, 48 GTS+ ADHD patients group among of them and 71 healthy controls. The correlation between positive association of polymorphism (val158met) of COMT gene in GTS and the age of onset in patients with GTS was also analyzed. Results Compared with healthy controls group, genotype of val158met did not differ in total GTS patients group or alone-GTS patients group (χ2=0.56, P=0.756; χ2=1.05, P=0.600 respectively). There was also no significant difference (P>0.05) in allele distribution of val158met in total GTS patients group or alone-GTS patients group compared with controls group respectively (χ2=0.18, P=0.669; χ2=0.29, P=0.593 respectively). However, genotype distribution of val158met was significantly different between GTS+ ADHD patients group and controls group(χ2=6.35, P=0.041). The frequency of the val allele of this locus was significantly higher in GTS+ ADHD patients group than those in controls group (χ2=5.49, P=0.019). The mean age of onset (6.80±1.54) in 36 children within GTS+ ADHD patients group with the val/val genotype of COMT gene val158met polymorphism was significantly earlier than the mean age of onset (8.04±1.54) in 12 children in val/val genotype(P=0.016). Conclusion Polymorphism (val158met) of COMT gene may be associated with GTS children with comorbid ADHD, which may play an important role to make the age of onset in children with GTS become earlier. Key words: Gilles de la Tourette's syndrome; Catechol-O-methyl transferase; Association analysis; Age of onset

Keine Assoziation zwischen Alexithymie und dem Catechol-O-Methyltransferase Val158Met-Polymorphismus

Reduced concentrations of dopamine in prefrontal brain structures may play a role in alexithymia. Dopamine degradation in the orbitofrontal cortex is regulated by catechol-O-methyltransferase (COMT), and a functional single nucleotide polymorphism of the COMT gene, Val158Met, has been related to psychiatric illness. This study examines the association between the COMT Val158Met gene polymorphism, and alexithymia. 120 healthy students and 120 patients with mental disorders were genotyped for the COMT Val158Met polymorphism. Additionally, the Toronto Alexithymia Scale (TAS-20) was administered. COMT genotype did not show a significant correlation with the TAS-20 in either group. COMT Val158Met polymorphism alone does not seem to be a major factor in alexithymia in healthy students. This is true even if patients with mental disorders covering a broader range of alexithymia are included. Thus, other genes, possibly interacting with cultural, environmental, and developmental factors, may be implicated.

Catechol- O-methyltransferase Val158Met polymorphism affects therapeutic response to mood stabilizer in symptomatic manic patients

Catechol-O-methyltransferase (COMT) is a candidate gene for the pathogenesis of some psychiatric disorders. The aim of this study is to examine the role of the COMT gene Val158Met polymorphism on the clinical aspects of bipolar disorder including symptomatology and therapeutic response. This study comprised 144 unrelated manic patients who met strict DSM-IV criteria for bipolar I disorder and 157 healthy unrelated controls. All subjects were of Korean ethnicity. To evaluate the clinical symptoms, we used the Young Mania Rating Scale at baseline and 6 weeks after treatment. No statistically significant difference in genotype distribution was found between manic patients and normal controls. There was also no significant difference in symptomatology among the genotypes in manic patients. In therapeutic response, however, patients with the Met/Met genotype were significantly more frequent in the non-responder than in the responder group. Our results suggest that the COMT gene polymorphism in the therapeutic response to mood stabilizers in manic patients. Further studies with a larger number of subjects and well-controlled design will be required to better understand the role of the COMT gene polymorphism on the therapeutic response to mood stabilizer in manic patients.

The COMT Val158Met polymorphism is associated with novelty seeking in czech methamphetamine abusers: Preliminary results

Background and aims:Measurable traits of human personality may mark the predisposition to psychopathology. Increased novelty seeking plays an important role in the pathogenesis of substance abuse. Novelty seeking, one of the fundamental traits of the human temperament, is related to dopamine. Catechol-O-methyltransferase (COMT) is essential for dopamine inactivation. The aim of our study was to assess whether the COMT gene Val158Met functional polymorphism in patients dependent on methamphetamine is related to their novelty seeking score.Methods:Patients dependent on methamphetamine who had been treated at the Addiction Treatment Unit in Nechanice in 2004 and 2005 agreed to participate in the investigation. We administered the Temperament and Character Inventory (TCI) questionnaire, assessed their novelty seeking score and analysed their DNA samples for COMT Val158Met genotype.Results:The subjects were thirty-seven Czech Caucasians (women N = 10) dependent on methamphetamine with an average age of 23.6 ± 3.8 years. We found a significantly higher mean novelty seeking score among the patients with the Met allele (Met/Met homozygotes + Val/Met heterozygotes; N = 28) than in nine Val/Val homozygotes (27.4 vs 24.1; p = 0.042, Two-Sample T-Test).Conclusions:The Met allele of the COMT gene Val158Met polymorphism is associated with low COMT enzyme activity and high endogenous dopamine synaptic levels in the prefrontal cortex. This leads to a decrease in dopaminergic neurotransmission in nucleus accumbens and a need for an increased activity to stimulate it. Novelty seeking behavior corresponds with this need.