Dopamine (DA), as a catecholamine neurotransmitter widely distributed in the central nervous system and the peripheral tissues, has attracted a lot of attention. Especially in recent years, DA has been found to regulate the function of the immune system, and the involvement of DA in the intestinal mucosal inflammation-related diseases has become a hot research topic. The digestive tract is an important source of peripheral DA, and DA is not only produced in the enteric nervous system and gastrointestinal epithelium, but also produced by intestinal microorganisms. In addition to the synthetases of DA, the DA contents in body tissues are also affected by the two kinds of metabolic enzymes, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). This article reviewed the sources, metabolism, and functions of DA in digestive tract, especially focusing on the distribution and function of MAO and COMT, the enzymes degrading DA.
Catechol O-Methyltransferase ; Catechol O-Methyltransferase Inhibitors ; Dopamine ; Gastrointestinal Tract ; Monoamine Oxidase ; Monoamine Oxidase Inhibitors

OBJECTIVE: We tested for association of the catechol-O-methyltransferase (COMT) Val158-Met (rs4680) polymorphism with attention-deficit hyperactivity disorder (ADHD) using family-based test in Korean trios. METHODS: A total of 181 subjects with ADHD along with both of their biological parents were recruited from University Hospitals in Korea. We performed a transmission disequilibrium test (TDT) on 181 trios. RESULTS: In the TDT, we found the over-transmission of the Val allele in children with ADHD (chi2=4.21, p=0.040). CONCLUSION: These results suggest that the COMT Val158-Met polymorphism is associated with ADHD among the Korean population. However, this study must be replicated in larger populations.
Alleles ; Catechol O-Methyltransferase* ; Child* ; Hospitals, University ; Humans ; Korea ; Parents

The enzyme catechol-O-methyltransferase (COMT) transfers a methyl group from S-adenosylmethionine to the benzene ring of catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. This review focuses on the association between the genetic polymorphisms of COMT gene and psychiatric disorders.
Catechol O-Methyltransferase ; genetics ; Humans ; Mental Disorders ; genetics ; Polymorphism, Genetic

OBJECTIVE: Many researches strongly suggest that early- and late-onset obsessive-compulsive disorder (OCD) represent separate subtypes of the disorder, possibly with distinct underlying pathogeneses. The aim of this study was to determine the association between Val-158-Met Catechol-O-Methyltransferase (COMT) genotypes and the onset of OCD. METHOD: We recruited 124 OCD patients and classified them into an early-onset group (age of onset < or = 17 years) and a late onset-group (age of onset >17 years). From the blood, DNA was isolated using standard techniques and the COMT Val-158-Met polymorphism (H/H, H/L, and L/L) was genotyped. Each genotype consists of H (high activity) allele and L (low activity) allele. Genotype and allele frequencies of early-and late-onset OCD were analyzed by chi-square statistics. RESULTS: The frequencies of H/H genotype and H allele in early-onset OCD group were significantly higher than late-onset OCD group (p=0.037 ; p=0.014). CONCLUSION: These results suggest that COMT gene polymorphism might be an important factor in the onset of OCD.
Alleles ; Catechol O-Methyltransferase* ; DNA ; Gene Frequency ; Genotype ; Humans ; Korea* ; Obsessive-Compulsive Disorder*

OBJECTIVES: Catechol-O-methyltransferase (COMT) gene has been identified as a positional and functional candidate gene of schizophrenia. Although specific mechanism of increasing schizophrenia susceptibility by this gene has not been well described yet, recent studies suggest that the valine allele of COMT Val158Met polymorphism may contribute to cognitive decline in schizophrenia. The present study investigated the association between this polymorphism of COMT gene and cognitive markers related to schizophrenia in both schizophrenia patients and normal controls. METHODS: The subjects were 78 patients with schizophrenia diagnosed by DSM-IV and 97 normal controls. Comprehensive neurocognitive tests for which performance deficits have been reported in schizophrenia were administered. Genotyping for COMT Val158Met polymorphism was done with SNapShot method. Association analyses between genotype and cognitive functions were performed using ANCOVA and MANCOVA. RESULTS: In the comparison of allele frequencies between patient and control groups, no significant association between the polymorphism and schizophrenia was observed. Significant differences of cognitive performance among genotype groups were not identified in control group. This trend was also observed in the patient group. In the combined analysis of both patient and control groups, there was no significant genotype or genotype-by group effect on any cognitive function measure. CONCLUSION: These findings do not support a major role of COMT gene in the regulation of the cognitive processes of schizophrenia.
Alleles ; Catechol O-Methyltransferase ; Cognition ; Diagnostic and Statistical Manual of Mental Disorders ; Gene Frequency ; Genotype ; Humans ; Schizophrenia ; Valine

OBJECTIVE: Catechol-O-methyltransferase(COMT) is an important enzyme that inactivates biologically active or toxic catechols. Abnormal catecholamine transmission has been implicated in the pathogenesis of schizophrenia and bipolar disorder. Polymorphism(Val/Met) of the COMT gene was shown to determine high-and low-activity alleles of the enzyme. This study was designed to investigate the association between COMT gene polymorphism and schizophrenia and bipolar disorder in a Korean population. METHOD: COMT gene were genotyped with polymerase chain reaction and restriction enzyme NlaIII in 128 patients with schizophrenia, 110 with bipolar disorder, and 176 controls. RESULTS: 1) The distribution of the COMT genotype in schizophrenic patients with Val/Val, Val/Met, Met/Met were 76(59.4%), 43(33.6%), 9(7.0%), in bipolar disorder patients were 63(57.3%), 35(31.8%), 12(10.9%), and in the controls were 83(47.2%), 79(44.9%), 14(8.0%). The allele frequencies of the COMT gene in schizophrenic patients with Val and Met were 195(76.2%), 61(23.8%), in bipolar disoreder patients were 161(73.2%), 59(26.8%), and in the controls were 245(69.6%), 107(30.4%). 2) There were no differences in genotype distribution and allele frequencies of COMT gene polymorphism among the 3 groups. Neither patients with schizophrenia nor bipolar disorder differed in the genotype and allelic frequencies from the controls. CONCLUSION: These results suggest COMT gene polymorphism is not causally related to the development of schizophrenia and bipolar disorder in a Korean Population.
Alleles ; Bipolar Disorder* ; Catechol O-Methyltransferase* ; Catechols ; Gene Frequency ; Genotype ; Humans ; Polymerase Chain Reaction ; Schizophrenia*

OBJECTIVES: We investigated whether the catechol-O-methyltransferase (COMT) and serotonin related gene polymorphisms may be associated with agoraphobia in patients with panic disorder in Korea. METHODS: The COMT gene (rs4680), 5-hydroxytryptamine (serotonin) transporter linked polymorphic region (5-HTTLPR) gene (rs25531), serotonin receptor 1A (HTR1A) gene (rs6295) genotypes were analyzed in 406 patients with panic disorder and age-sex matched 206 healthy controls. Patients with panic disorder were dichotomized by the presence of agoraphobia. The following instruments were applied : the Beck Depression Inventory, the Beck Anxiety Inventory, the Panic Disorder Severity Scale. RESULTS: There was a significant difference in the distribution of 5-HTTLPR genotype between panic patients with agoraphobia and without agoraphobia (p = 0.024). That is, the panic patients with agoraphobia had a significant excess of the less active 5-HTTLPR allele (S allele). (p = 0.039) Also, we replicated previous western reports which indicated a significant difference in the distribution of COMT genotype between the patients with panic disorder and the healthy controls (p = 0.040). However, no significant associations of agoraphobia or panic disorder with HTR1A gene polymorphisms were found. CONCLUSIONS: This result supports that the COMT polymorphisms may be associated with panic disorder and suggests that the 5-HTTLPR polymorphisms may play a role in the pathogenesis of agoraphobia in the Korean patients with panic disorder.
Agoraphobia ; Alleles ; Anxiety ; Catechol O-Methyltransferase ; Depression ; Genotype ; Humans ; Korea ; Panic Disorder* ; Panic* ; Serotonin

OBJECTIVES: Common genetic SNPs in two genes, encoding catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR), which are interconnected with COMT gene regulation, have been reported to contribute to schizophrenia risk. In this study, we evaluated the association between functional polymorphisms in COMT and MTHFR and schizophrenia risk with a case-control study in a Korean population. METHODS: We performed a case-control study by genotyping analysis using 360 cases and 348 controls in Korean subjects to determine the association between functional polymorphisms in COMT and MTHFR and schizophrenia risk. RESULTS: Four functional SNPs in COMT (Val158Met and rs165599) and MTHFR (C677T and A1298C) were genotyped by primer extension assay. None of the genotype distributions for the four SNPs was significantly different between cases and controls. Stratified analysis did not show any significant gender difference for any polymorphism. In addition, we found no evidence of a gene-gene interaction in the analysis of combined genotypes. CONCLUSION: Our results suggest no significant association between the selected functional polymorphisms of COMT or MTHFR in Korean schizophrenia subjects. However, further studies are required to confirm our findings in a larger number of subjects.
Case-Control Studies ; Catechol O-Methyltransferase ; Genotype ; Methylenetetrahydrofolate Reductase (NADPH2) ; Polymorphism, Single Nucleotide ; Schizophrenia

OBJECTIVE: To examine the relationship between COMT polymorphisms and the response to antipsychotic drugs, and then provide a basis for personalized medicine of antipsychotic drugs.
 METHODS: We performed a systematic search from PubMed, Embase, Cochrane Library, CBM, CNKI, VIP and Wanfang database for eligible studies. Stata 12.0 was used for Meta-analysis after evaluating the quality of studies and collecting the data.
 RESULTS: Nine studies included 868 participants met inclusion criteria. Significant association was found between the COMT Val108/158Met gene polymorphism and antipsychotic drug efficacy. Evaluating the therapeutic efficacy through general symptoms: Met vs Val, RR=1.18, 95% CI: 1.04-1.35, P=0.013; Met/Met vs Val/Val, RR=1.40, 95% CI: 1.08-1.82, P=0.010. Evaluating the therapeutic efficacy through negative symptoms: Met vs Val, RR=1.24, 95% CI: 1.05-1.46, P=0.013; Met/Met vs Val/Val, RR=1.60, 95% CI: 1.04-2.46, P=0.031.
 CONCLUSION COMT Val108/158Met gene polymorphism is significantly associated with antipsychotic drug efficacy, and Met gene is a dominant gene which displays a better response to antipsychotic drugs.
Antipsychotic Agents ; therapeutic use ; Catechol O-Methyltransferase ; genetics ; Humans ; Polymorphism, Genetic

The prevalence of violence behavior in patients with schizophrenia is higher than that in common population. Data suggest that genetic factors may play a substantial role for the etiology of the behavior. Among the particular gene polymorphisms that have been considered to be involved in violence behavior, the catechol-O-methyltransferase (COMT) gene had been the focus of recent research. This article reviews the association research between COMT gene and violence behavior in patients with schizophrenia in several aspects: SNP polymorphism of COMT Val158Met and COMT Ala72Ser, haplotype of COMT gene and DNA methylation of promoter region of COMT gene. The genetic research direction is presented for patients with schizophrenia.
Aggression ; Catechol O-Methyltransferase/genetics* ; Haplotypes ; Humans ; Polymorphism, Genetic ; Schizophrenia/genetics* ; Violence