catechol-O-methyltransferase Gene Polymorphism Research Articles

The influence of COMT and ABCB1 gene polymorphisms on sufentanil analgesic effect for postoperative pain in children with fracture.

The aim of this observational study was to investigate the effects of catechol-O-methyltransferase (COMT) and ATP-binding cassette transporter B1 (ABCB1) gene polymorphisms on the postoperative analgesic effect of sufentanil in Chinese Han pediatric patients with fractures. A total of 185 pediatric patients who underwent fracture surgery were included. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphisms of COMT and ABCB1 genes. Sufentanil was used for postoperative analgesia. The pain level of the patients was evaluated using the face, legs, activity, cry, and consolability scale before surgery, during awakening, at 2, 6, 12, and 24 hours after surgery. The postoperative Ramsay sedation score, sufentanil consumption, and incidence of adverse reactions were also recorded. Pediatric patients with different genotypes of ABCB1 and COMT showed no statistically significant differences in general data such as age, gender, weight, height, surgical duration, and American Society of Anesthesiologists classification (P > .05). There were no statistically significant differences in sedation scores after surgery between different genotypes of ABCB1 and COMT (P > .05). Among patients with CC genotype in ABCB1, the pain scores and total consumption of sufentanil at awakening, 2 and 6 hours after surgery were higher compared to TT and CT genotypes (P < .05), while there were no statistically significant differences between TT and CT genotypes (P > .05). Among patients with AA genotype in COMT, the pain scores and total consumption of sufentanil at awakening, 2, 6, 12, and 24 hours after surgery were higher compared to AG and GG genotypes (P < .05), while there were no statistically significant differences between AG and GG genotypes (P > .05). There were no statistically significant differences in adverse reactions between different genotypes of ABCB1 and COMT (P > .05). The polymorphisms of COMT gene rs4680 and ABCB1 gene rs1045642 are associated with the analgesic effect and consumption of sufentanil in pediatric patients after fracture surgery.

Udruženost polimorfizama gena za katehol-Ometiltransferazu sa terapijskim odgovorom i komplikacijama izazvanim levodopom kod Parkinsonove bolesti - rezime sadašnjih saznanja

Catechol-O-methyltransferase (COMT) is one of the cardinal enzymes in the degradation of catecholamines and levodopa. Genetic variants of the COMT gene may affect COMT enzyme activity. The most examined COMT gene polymorphism is the nonsynonymous single nucleotide polymorphism (SNP) in exon 4 (Val108/158Met; rs4680). This highly functional polymorphism is responsible for fourfold variations in enzyme activity and Dopamine catabolism. Recent data suggested that even synonymous SNPs of the COMT gene can lead to changes in enzyme activity. Genetically determined COMT activity can affect an individual's response to levodopa therapy and carries the risk of complications from prolonged levodopa use in Parkinson's disease (PD) patients. Identifying at-risk individuals through genetic susceptibility markers could help to prevent the development of levodopa-induced complications in PD.

Associations between Catechol-O-methyltransferase (COMT) polymorphisms and cognitive impairments, psychiatric symptoms and tardive dyskinesia in schizophrenia

IntroductionCatechol-O-methyltransferase (COMT) is a crucial enzyme involved in dopamine metabolism and has been implicated in the etiology of tardive dyskinesia (TD). We aimed to investigate the associations between COMT gene polymorphisms and the occurrence and severity of TD in a Chinese population, as well as the impact on the psychiatric symptoms and cognitive impairments observed in TD patients. MethodsA total of 216 chronic schizophrenia patients, including 59 TD patients and 157 NTD patients, were recruited for this study. Three SNPs of the COMT gene (rs4680, rs165599 and rs4818) were selected and genotyped using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). TD severity, psychopathology and cognitive functioning were assessed using the Abnormal Involuntary Movement Scale (AIMS), the Positive and Negative Syndrome Scale (PANSS) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively. ResultsIn TD patients, total AIMs scores were higher in carriers of the rs4680 AA genotype than in carriers of the AG and GG genotypes (p = 0.01, 0.006), carriers of the rs4818 GC and CC genotypes had higher orofacial scores than in GG genotypes (p = 0.032, 0.002). In male TD patients, carriers of the rs165599 GA genotype scored lower in the extremities and trunk scores than AA genotype carriers (p = 0.015). Moreover, in male TD patients, COMT rs4818 was associated with cognition, since the C allele carriers had significantly higher immediate memory (p = 0.043) and verbal function (p = 0.040) scores than the G allele carriers. In addition, rs165599 genotype interacted with TD diagnosis on depressed factor (p = 0.031). ConclusionWithin the Chinese population, COMT gene polymorphisms could potentially serve as biomarkers for the symptoms and prognosis of TD patients.

Relationship between COMT Gene Polymorphism, Anxiety, and Pain Perception during Labour.

The COMT gene polymorphism is associated with neurological and psychiatric disorders and pain perception. The present study investigates the existence of anxiety and pain perception in relation to the COMT (catechol-O-methyltransferase) gene polymorphism in labouring women (during "natural" childbirth) with or without inhaled analgesia. A total of 181 women who chose vaginal birth were enrolled in this study. To present the difference in pain perception, the parturients were divided into one group (n = 90) that chose labour analgesia with inhaled nitrous oxide (50% nitrous oxide and 50% oxygen) and one group (n = 91) without analgesia. The blood samples were taken during the pregnancy as a part of routine pregnancy controls in the hospital. The COMT gene polymorphism was detected with the PCR technique. The pain perception of parturients was self-evaluated two times according to the VAS (Visual Analogue Scale), and anxiety as a personality trait was determined with the STAI-T (State Trait Anxiety Inventory). Pain perception as well as anxiety were compared according to COMT genotypes. In the 181 pregnant women, there were 40 women (22%) of wild homozygotes (GG) of COMT, 95 women (53%) of mutant heterozygotes (GA), and 46 women (25%) of mutant homozygotes (AA). A negative association of pain perception with the GA (mutant heterozygote) polymorphism of the COMT gene versus the wild-type (GG polymorphism) was observed. The GA polymorphism of the COMT gene was associated with 0.46 units lower pain perception compared to the wild type (GG). The anxiety trait score in group AA was lower than in groups GA and GG. The difference reached statistical significance only when comparing AA versus GA (p > 0.042). Analgesic efficacy of nitrous oxide was noticed in 22% of labouring women who reported moderate pain (VAS score 4-7). The COMT gene polymorphism was associated with pain perception and anxiety among parturients. The COMT gene polymorphism GA was associated with negative pain perception among labouring women. Nitrous oxide showed statistical significance in anxiolytic efficacy during labour in women with mild anxiety as a personality trait. Anxiolytic efficacy of nitrous oxide has shown better efficacy in parturients with the COMT gene polymorphism AA.

Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson's Disease: A Meta-Analysis and Systematic Review.

Long-term levodopa therapy for Parkinson's disease (PD) can cause levodopa induced dyskinesia (LID). Genetic predisposition has a significant role to play in inter-individual heterogeneity in the clinical manifestation of LID. Despite accumulating evidence for the role of COMT gene polymorphism (rs4680) as a genetic basis for LID, to date results have been inconsistent. Early assessment of the Catechol-O-Methyltransferase (COMT) genotype might be helpful to stratify PD patients concerning their individual risk for LID. In this meta-analysis, we have used 9 studies, which were selected through online databases. Statistical analysis was performed using R (v-3.6) software. 5 genetic models have been used in the present study: Allele model (A vs. G), Dominant model (AA+AG vs. GG), Homozygote model (AA vs. GG), Co-dominant/heterozygote model (AG vs. GG), and Recessive model (AA vs. AG + GG). The results indicated a significant association between COMT rs4680 (Val158Met) polymorphism and LID risk. The genotype AA of COMT rs4680 is a risk factor for LID in PD patients under the recessive model (AA vs GG+AG) in the random-effect model. Analysis based on ethnicity showed that COMT rs4680 SNP allele A is a risk factor for LID development in Asian PD patients, while GG genotype is a risk factor for LID development in non-Asian PD patients using different genetic models. The results of the present meta-analysis support that the COMT Val158Met polymorphism is a risk factor for the development of LID in PD patients having ethnic variations.

Influence of COMT (rs4680) and DRD2 (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of COMT (rs4680) and DRD2 (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of COMT (rs4680) (p = 0.04994) in all ADHD children. No effect of COMT (rs4680) and DRD2 (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed DRD2 and COMT gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity COMT (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.

Val158Met polymorphisms of COMT gene and serum concentrations of catecholaminergic neurotransmitters of ADHD in Chinese children and adolescents.

This study analyzed the Val158Met polymorphisms of the catechol-O-methyltransferase (COMT) gene and serum concentrations of catecholaminergic neurotransmitters in attention deficit hyperactivity disorder (ADHD) children and adolescents.All the subjects (180 paired ADHD and non-ADHD children and adolescents) were genotyped for the Val158Met polymorphisms of the COMT gene, and determined by the difference of dopamine and noradrenalin from a 1:1 paired case–control study.The frequencies of methionine (A)/A, valine (G)/A, and G/G were 51.67%, 41.11%, and 7.22% in the case group, and 62.22%, 31.11%, and 6.67% in the control group. There was a significant difference in the distribution of all genotypes of the COMT gene between the 2 groups (odds ratio = 1.85, 95% confidence interval: 1.62–2.08; χ2 = 7.80, P < .05). The serum concentrations of dopamine and noradrenalin were 1.42 ± 0.34 ng/mL and 177.70 ± 37.92 pg/mL in the case group, and 1.94 ± 0.42 ng/mL and 206.20 ± 42.45 pg/mL in the control group. There were the significant differences in the levels of dopamine and noradrenalin between the 2 groups (dopamine: t = 4.30, P < .01; noradrenalin: t = 2.24, P < .05).Our study suggested that the Val158Met polymorphisms of the COMT gene and serum concentrations of catecholaminergic neurotransmitters were associated with ADHD children and adolescents.

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.

Long acting aripiprazole influences cognitive functions in recent onset schizophrenia.

Beneficial effects of aripiprazole on cognition in schizophrenia have been previously reported, but not in recent onset schizophrenia. Cognitive impairments have also been associated with catechol-O-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and serotonin transporter (SERT) gene polymorphisms which were earlier implicated in the pathophysiology of schizophrenia. This study examined the short-term influence of aripiprazole long-acting injectable (LAI) as well as of COMT, MTHFR, and SERT gene polymorphisms and their interactions on clinical features and cognitive functions in inpatients with recent onset schizophrenia. This study included 98 inpatients suffering from recent onset schizophrenia diagnosed according to DSM-5 criteria. Three months after initiating aripiprazole LAI, the severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), while cognitive functions were measured by 5-KOG test for cognition. Genotypes of SERT, MTHFR, and COMT gene were determined by different polymerase chain reaction (PCR) methods. Three-month aripiprazole LAI treatment was associated with a statistically significant change of PANSS total (p<0.001) and subscale scores as well as cognitive parameters of delayed recall (p<0.03), attention (p<0.01), and executive functions in the form of less perseverations (p<0.03), without influencing other examined cognitive functions. However, it significantly influenced composite cognitive score (p<0.02). In regard to the investigated genetic polymorphisms, we established a positive association between the COMT polymorphism (M/M allele carriers) and attention (p<0.01). Additionally, we also established a positive association between the COMT - MTHFR interaction and attention (p<0.02), as well as perseveration item belonging to executive functions (p<0.01). Two other investigated polymorphisms (MTHFR and SERT) were not significantly associated with cognitive indices. Investigated genetic polymorphisms and their interactions were not associated with PANSS scores. Our findings suggest that aripiprazole LAI improves individual cognitive functions in recent onset schizophrenia. Investigated COMT polymorphism (Met/Met genotype), as well as the COMT-MTHFR interaction, were positively associated with attention and executive functioning (perseveration), potentially implying COMT's biomarker potential in terms of cognition in schizophrenia.

First Demonstration of Double Dissociation between COMT-Met158 and COMT-Val158 Cognitive Performance When Stressed and When Calmer.

We present here the first evidence of the much-predicted double dissociation between the effect of stress on cognitive skills [executive functions (EFs)] dependent on prefrontal cortex (PFC) by catechol-O-methyltransferase (COMT) genotype. The COMT gene polymorphism with methionine (Met) at codon 158 results in more dopamine (DA) in PFC and generally better EFs, while with valine (Val) at codon 158 the result is less PFC DA and generally poorer EFs. Many have predicted that mild stress, by raising PFC DA levels should aid EFs of COMT-Vals (bringing their PFC DA levels up, closer to optimal) and impair EFs of COMT-Mets (raising their PFC DA levels past optimal). We tested 140 men and women in a within-subject crossover design using extremely mild social evaluative stress. On trials requiring EFs (incongruent trials) of the Flanker/Reverse Flanker task, COMT-Val158 homozygotes performed better when mildly stressed than when calmer, while COMT-Met158 carriers performed worse when mildly stressed. Two other teams previously tried to obtain this, but only found stress impairing EFs of COMT-Mets, not improving EFs of COMT-Vals. Perhaps we found both because we used a much milder stressor. Evidently, the bandwidth for stress having a facilitative effect on EFs is exceedingly narrow.

In Silico Prediction of the Effects of Nonsynonymous Single Nucleotide Polymorphisms in the Human Catechol-O-Methyltransferase (COMT) Gene.

Catechol-O-methyltransferase (COMT) enzyme performs transfer of methyl group to endogenous and exogenous catechol substrates. The COMT enzyme draws interest because of its association with psychiatric, neurological and cardiovascular diseases, and several cancers. Moreover, many prescribed drugs, supplements, and their metabolites are used as substrates of COMT enzyme. The human COMT gene has 226 nonsynonymous single nucleotide polymorphisms (nsSNPs) according to public databases. Uncovering of the molecular impacts of nsSNPs on COMT enzyme function and structure may provide standpoint on how COMT nsSNPs affect enzyme activity and contribute to disease development. Therefore, we aimed in this study to predict possible structural and functional damaging effects of all knowns nsSNPs in COMT gene by applying various bioinformatics tools. Two hundred and twenty-six nsSNPs were obtained from Ensembl, HGMD, ClinVar, and dbSNP databases. Twenty-eight nsSNPs were found to be high-risk changes for protein structure. Some of them were detected in extremely conserved sequences have functional and structural properties. Besides, high-risk nsSNPs were also uncovered to change properties of native COMT protein. Our findings demonstrated the significance of COMT high-risk nsSNPs on protein structure and function. We expect that our results will be helpful in future studies concerning experimental evaluation of the COMT gene polymorphisms and/or the association between COMT polymorphisms and disease development.

Effects of traumatic life events, cognitive biases and variation in dopaminergic genes on psychosis proneness.

Recent studies have provided evidence that interactions between variation in dopaminergic genes and stressful experiences might impact risk of psychosis. However, it remains unknown whether these interactions impact the development of subclinical symptoms, including psychotic-like experiences (PLEs). In this study, we aimed to test the effects of interactions between variation in dopaminergic genes and traumatic life events (TLEs) on a severity of PLEs. We assessed TLEs, cognitive biases, PLEs as well as the catechol-O-methyltransferase (COMT) rs4680 and the dopamine D2 receptor (DRD2) rs6277 gene polymorphisms in 445 university students at three urban areas. There was a significant effect of the interaction between the COMT rs4680 and a history of any type of TLEs on a severity of PLEs. Among the COMT rs4680 Met allele carriers, a severity of PLEs was higher in individuals with a history of any type of TLEs. Further stratification of the sample revealed that this effect appears only in the group of participants with a high level of cognitive biases. The DRD2 rs6277 C allele was independently associated with a higher level of PLEs. Our results indicate that decreased dopamine catabolism related to the COMT gene polymorphism might increase psychosis proneness in individuals with a history of TLEs and high levels of cognitive biases. Variation in the DRD2 gene might exert independent effects on psychosis proneness. These findings imply that there are various levels of complexity in the models of interactions between genetic and environmental factors explaining the mechanisms underlying psychosis proneness.

The Association of Catechol-O-Methyl-Transferase and Interleukin 6 Gene Polymorphisms with Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a disorder that occurs in some people who have experienced a severe traumatic event. Several genetic studies suggest that gene encoding proteins of catechol-O-methyl-transferase (COMT) may be relevant for the pathogenesis of PTSD. Some researchers suggested that the elevation of interleukin-6 (IL6) correlates with major depression and PTSD. The aim of this study was to investigate whether the single nucleotide polymorphisms COMT rs4680 (Val158Met) and IL6 rs1800795 are associated with PTSD and contribute to the severity of PTSD symptoms. This study comprised 747 participants that experienced war between 1991 and 1999 in the South Eastern Europe conflicts. COMT rs4680 (Val158Met) and IL6 rs1800795 genotypes were determined in 719 participants (369 with and 350 without PTSD). The Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) questionnaire and the Brief Symptom Inventory (BSI) were used for data collection. Regarding the COMT gene polymorphism, the results of the regression analyses for BSI total score were significant in the lifetime PTSD group in the dominant (P=0.031) and the additive allelic model (P=0.047). Regarding the IL6 gene, a significant difference was found for the recessive model predicting CAPS total score in the lifetime PTSD group (P=0.048), and indicated an association between the C allele and higher CAPS scores. n the allelic, genotypic and rezessive model, the results for BSI total score were significant in the lifetime PTSD group (P=0.033, P=0.028 and P=0.009), suggesting a correlation of the C allele with higher BSI scores. Although our nominally significant results did not withstand correction for multiple tests they may support a relevance of the COMT (Val158Met) and IL6 rs1800795 polymorphism for aspects of PTSD in war traumatized individuals.

COMT polymorphism regulates the hippocampal subfield volumes in first-episode, drug-naive patients with major depressive disorder.

Purpose: Compared with healthy subjects (HS), patients with major depressive disorder (MDD) exhibit volume differences that affect the volume changes in several areas such as the limbic, cortical, subcortical, and white matter. Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes endogenous catecholamines. The Val158Met polymorphism of COMT has been reported to affect the dopamine (DA) levels, which plays an important role in psychiatric diseases. However, the relationships among both DA levels, COMT genotype, and brain morphology are complicated and controversial. In previous studies that investigated the hippocampal subfields, the greatest brain abnormalities in MDD patients were observed in Cornu Ammonis (CA)1 and the subiculum, followed by that in CA2-3. We have prospectively demonstrated the relationship between the single-nucleotide polymorphism of the Val158Met COMT gene (rs4680) and the hippocampal subfields in drug-naive MDD patients.Patients and methods: In this study, we compared 27 MDD patients and 42 HS who were divided into groups based on their COMT genotype. The effects of the diagnosis, genotype, and genotype–diagnosis interaction related to CA1 and the subiculum volumes, as well as the whole-brain cortical thickness, were evaluated by performing a FreeSurfer statistical analysis of high-resolution magnetic resonance imaging (MRI) findings.Results: The results revealed that there was a statistically significant interaction between the effects of diagnosis and genotype on the right subiculum (a component of the hippocampus).Conclusion: This Val158Met COMT polymorphism may influence the subiculum volume in drug-naive, first-episode MDD patients.

Interaction Between Environmental Risk Factors and Catechol-O-Methyltransferase (COMT) and X-Ray Repair Cross-Complementing Protein 1 (XRCC1) Gene Polymorphisms in Risk of Lung Cancer Among Non-Smoking Chinese Women: A Case-Control Study.

BackgrpoundVarious studies have highlighted the link between polymorphisms in the XRCC1 gene (encoding X-ray repair cross-complementing group 1) with the incidence of decreased DNA repair capacity and an increased predisposition to cancer. Catechol-O-methyltransferase (COMT) plays a crucial role in estrogen-induced cancers. In the present study was analyzed the potential influence of XRCC1 and COMT gene polymorphisms as predisposing factors from a lung cancer perspective, in addition to conducting an investigation into their interaction with environmental risk factors in relation to lung cancer among non-smoking Chinese women.Material/MethodsThe XRCC1 gene T-77C, Arg194Trp, Arg280His, Arg399Gln, COMT gene 186C>T, and Val158Met mutations were evaluated in peripheral blood collected from 261 non-smoking female patients diagnosed with primary lung cancer and 265 female patients with benign lung disease.ResultThe results obtained from this study demonstrated that XRCC1–77TC + CC, XRCC1 399Gln/Gln, COMT 186CT + TT, COMT 158Val/Met genotypes, type of occupation, cooking-oil fumes, and soot exposures were all independent risk factors involved with the occurrence of lung cancer among non-smoking women. Moreover, interactions between environmental exposure factors as well as XRCC1 and COMT gene polymorphisms were determined to play significant contributory roles regarding susceptibility of non-smoking females to lung cancer.ConclusionsTaken together, T-77C and Arg399Gln polymorphisms of the XRCC1 gene, as well as the 186C>T and Val158Met polymorphisms of the COMT gene, increased the risk of lung cancer in non-smoking women, with the factors of occupation type, cooking-oil fumes, and soot exposures representing key contributing factors.

Association between COMT gene polymorphisms, clinical symptoms, and cognitive functions in Han Chinese patients with schizophrenia

Catechol-O-methyltransferase (COMT) gene variants may be involved in the pathogenesis of psychotic symptoms, and associated especially with negative symptom in schizophrenia, but their roles in cognitive function and treatment response remain unclear. The aim of this study was to explore the association between COMT gene polymorphisms, clinical symptoms (including cognitive function), and treatment response to antipsychotic medications in patients with schizophrenia. A total of 200 Han Chinese inpatients with schizophrenia were recruited in accordance with Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). In total, 96 of them completed assessments at baseline and after 8 weeks of antipsychotic treatment. Clinical symptoms were assessed using the Positive And Negative Syndrome Scale (PANSS), and cognitive function was evaluated using the Verbal Fluency Test, Trail Making Test A-B, Stroop Color-Word Test, and Wisconsin Card Sorting Test. Two single nucleotide polymorphisms, rs4680 and rs165599, on the COMT gene were genotyped. At baseline, we found no significant genotypic association between rs4680 and clinical symptoms or cognitive function. After 8 weeks of antipsychotic treatment, compared with patients with GG genotype, patients with AA/AG genotypes at rs4680 showed significantly higher scores on PANSS total, both at baseline and at the end of 8 weeks, especially in negative and general psychopathology symptoms. Patients with GG at rs165599 scored significantly higher on the Stroop test, suggesting better cognitive performance after 8 weeks of treatment. No significant association was found between rs165599 genotype and psychiatric symptoms as assessed by the PANSS and cognitive function tests at baseline. Our findings suggest that the COMT gene polymorphisms may influence the response to antipsychotic treatment in Han Chinese patients with schizophrenia.

Differential effect of COMT gene methylation on the prefrontal connectivity in subjects with depression versus healthy subjects

Expression of the catechol-O-methyl transferase (COMT) gene mainly determines prefrontal dopaminergic availability. Deficient prefrontal dopaminergic activity leads to loss of interest, energy, and motivation, which are core symptoms of depression. Given the role of stress-environmental interactions in major depressive disorder (MDD), we investigated the impact of COMT gene methylation status on prefrontal connectivity. We measured COMT gene methylation and polymorphisms (Val158Met) at the rs4468 locus in peripheral blood samples of healthy controls (n = 90) and patients with MDD (n = 90). We used diffusion tensor imaging to calculate the fractional anisotropy (FA) and radial diffusivity (RD) of the white matter tracts related to prefrontal cortex. Finally, we examined the effects of COMT gene methylation on the white matter connectivity in patients with MDD. The FA and RD values in the prefrontal white matter tracts of patients with MDD were positively and negatively associated with COMT gene methylation, respectively. In the control group, on the other hand, the association between white matter connectivity and COMT gene methylation showed opposite pattern to those of MDD. COMT gene methylation has a substantial effect on the prefrontal connectivity in patients with MDD. Moreover, COMT gene methylation and prefrontal connectivity showed opposite relationships in patients and controls. Thus, stress-related alterations in dopaminergic neurotransmission have a differential effect on white matter connectivity according to the microenvironment in the brain.

The influence of dopamine-beta-hydroxylase and catechol O-methyltransferase gene polymorphism on the efficacy of insulin detemir therapy in patients with type 2 diabetes mellitus

BackgroundType II diabetes is an important health problem with a complex connection to obesity, leading to a broad range of cardiovascular complications. Insulin therapy often results in weight gain and does not always ensure adequate glycemic control. However, previous studies reported that insulin detemir is an efficient long-acting insulin with a weight sparing effect. The aim of this study was to determine the association of catechol O-methyltransferase (COMT) Val108/158Met and dopamine-beta-hydroxylase (DBH) 1021C/T polymorphisms with the effectiveness of insulin detemir in achieving glucose control and body weight control. Participants and methods: This 52-week observational study included 185 patients with inadequate glycemic control treated with premix insulin analogues, which were replaced with insulin aspart and insulin detemir, and 156 healthy controls. After DNA isolation from blood samples, genotyping of DBH-1021C/T polymorphism (rs1611115) and COMT Val108/158Met polymorphism (rs4680) was performed.ResultsOur results confirmed that insulin detemir did not lead to weight gain. The most significant finding was that A carriers (the combined AG and AA genotype) of the COMT Val108/158Met achieved significantly better hemoglobin A1c (HbA1c) values compared to patients carrying GG genotype. No association between DBH-1021C/T genotypes and weight and/or glucose control was detected in diabetes patients or in healthy control subjects.ConclusionsThis study showed that the presence of one or two A allele of the COMT Val108/158Met was associated with improved glycemic response, and with a better response to insulin detemir therapy in patients with type II diabetes, separating them as best candidates for detemir therapy.

Association Studies of DRD2 and COMT Gene Polymorphisms with Risperidone-induced Amenorrhea in Female Schizophrenia Patients

Object: To study the association between dopamine D2 receptor (DRD2) and catechol-O-methyltransferase (COMT) gene polymorphisms and the risperidone-induced amenorrhea resulted from hyperprolactinemia in female schizophrenia patients. Patients and methods: According to International Diagnostic and Classification of Diseases tenth edition (ICD-10) criteria, 45 Chinese female schizophrenic patients (25 patients with amenorrhea, and 20 patients with eumenorrhea) were recruited by trained psychiatrists in this study. Sanger sequencing was utilized to determine the DRD2 and COMT genotypes from peripheral venous blood samples. Results: There were no significant differences between amenorrhea patients and eumenorrhea patients in age, disease courses and risperidone dosages (P>0.05). Also, no significant differences were observed in rs6277, rs1079598 and rs4680 polymorphisms between the two groups. Conclusion: These results suggest that DRD2 rs6277, rs1079598 and COMT rs4680 gene polymorphisms show no significant correlation with risperidone-induced amenorrhea in Chinese female schizophrenia patients.

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.