Association between COMT and 5-HTTLPR Polymorphisms in Korean Patients with Panic Disorder : A Replication Study

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.

Association analysis of catechol-O-methyltransferase gene polymorphisms with schizophrenia in southern Chinese population / 中华行为医学与脑科学杂志

Objective To explore the association of catechol-O-methyhransferase(COMT) gene polymorphisms with schizophrenia susceptibility and its symptoms assessed by Positive and Negative Syndrome Scale (PANSS)in southern Chinese population.Methods COMT gene rs4633,rs4680 and rs8185002 polymorphisms were genotyped using Sequenom genotyping technology in 700 schizophrenia patients (300 Zhuang and 400 Han) and 700 healthy controls (300 Zhuang and 400 Han),and Positive and Negative Syndrome Scale (PANSS) was used for clinical symptoms assessment of patients.Statistical analysis was performed using PLINK software.Results rs4633,rs4680 and rs8185002 polymorphisms were not significantly associated with schizophrenia susceptibility in Zhuang or Han population respectively(P＞0.05).After merging Zhuang and Han samples,rs4633(I 2 =0.000,Pmeta =0.040) and rs4680 (I2=0.000,Pmeta =0.014) were significantly associated with the susceptibility to schizophrenia.In addition,haplotype T-A-T was significantly associated with schizophrenia susceptibility (P=0.049).However,these three polymorphisms were not significantly associated with total score,positive scale score,negative scale score and general psychopathology scale score assessed by PANSS(P＞0.05).Conclusion COMT gene rs4633 and rs4680 polymorphisms are involved in the susceptibility to schizophrenia in southern Chinese population.

Polimorfismo en el gen COMT en una muestra de gestantes normales y con restricción del crecimiento intrauterino en un hospital de Lima / COMT gene polymorphism in a sample of pregnant women with intruterine growth restriction in a Lima hospital

Antecedentes: Los procesos fisiopatológicos que ocurren a nivel celular y molecular en la restricción de crecimiento intrauterino (RCIU) son aún desconocidos. La catecol-O-metiltransferasa (COMT) es una enzima de fase II que inactiva los catecol estrógenos al transferir un grupo metílico. Se conoce un polimorfismo funcional Val158 Met en el gen COMT como un marcador susceptible para diversas enfermedades maternoperinatales, existiendo estudios que sugieren que el alelo que codifica una COMT de baja actividad puede ser un marcador susceptible para RCIU. Por lo tanto, el estudio del polimorfismo COMT ofrece una nueva estrategia para la evaluación de marcadores genéticos que pueden ser utilizados para la detección de ciertas alteraciones asociadas al embarazo. Objetivos: Establecer la asociación entre el polimorfismo Val158Met catecol-O-metiltransferasa (COMT) y la restricción de crecimiento intrauterino. Institución: Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Diseño: Estudio tipo relacional (asociativo), con diseño observacional, tipo caso-control (no experimental). Materiales: Muestra de sangre materna de parturientas. Métodos: Durante el año 2011, se obtuvo 81 muestras para genotipaje del gen COMT. De ellas, 26 (32,1%) correspondieron a parturientas con RCIU (casos) y 55 (67,9%) a muestras de madres de hijos sin RCIU (controles). La distribución de los genotipos fue evaluada usando la prueba de chi cuadrado. Se comprobó la distribución proporcional de los genotipos en los grupos con RCIU y sin RCIU con la hipótesis nula de Hardy-Weinberg. Las madres participantes firmaron un consentimiento informado. Principales medidas de resultados: Asociación entre los genotipos COMT y la RCIU, y entre los alelos COMT Val/Met y la RCIU. Resultados: Las distribuciones de los genotipos en los grupos con RCIU y sin RCIU estuvieron de acuerdo a la hipótesis nula de Hardy-Weinberg. Al relacionar los genotipos COMT Val/Met con la condición de RCIU, la prueba X²=1.8057, gl=2, p=0.4054, no encontró asociación entre dichos genotipos y la RCIU. Al determinar la asociación entre los alelos COMT y la RCIU, tampoco se encontró asociación entre los alelos COMT Val/Met y la condición de RCIU en la muestra estudiada, con prueba X²=0.3659, gl=1, p=0.5453. Conclusiones: No se encontró asociación entre los genotipos COMT y la RCIU, ni entre los alelos COMT Val/Met y la RCIU, en la muestra estudiada.

Background: Cellular and molecular events in the pathophysiology of intrauterine growth restriction (IUGR) are still unknown. Cathecol O-methyltransferase (COMT) is a phase II enzyme that inactivates cathecol estrogens by transferring a methyl group. A functional polymorphism Val158 Met in COMT gene is known as susceptible marker for diverse maternal and perinatal diseases, and studies suggest the allele codifying a low activity COMT may be a susceptible marker for IUGR. COMT polymorphism study may be a new strategy to determine genetic markers that might be used for detection of certain disorders related to pregnancy. Objectives: To determine association of Val158Met cathecol-O-methyltransferase (COMT) polymorphism and intrauterine growth restriction. Setting: Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Design: Relational (associative), observational, case-control (non-experimental) study. Materials: Maternal blood samples obtained following delivery. Methods: During 2011, 81 blood samples were obtained from post partum mothers for COMT gene genotyping, 26 (32.1%) were mothers with IUGR (cases) and 55 (67.9%) without IUGR (controls). Genotype distribution was determined by chi square test. Genotypes proportional distribution in IUGR and non-IUGR groups was determined with Hardy-Weinberg’s null hypothesis. All women signed informed consent. Main outcome measures: Association of COMT genotypes and IUGR, and between COMT Val/Met alleles and IUGR. Results: Genotype distribution in IUGR and non-IUGR groups agreed with Hardy-Weinberg null hypothesis. There was no association of COMT Val/Met genotypes and IUGR, X²=1.8057, gl=2, p=0.4054. There was no association between COMT Val/Met alleles and IUGR, X²=0.3659, gl=1, p=0.5453. Conclusions: No association was found either between COMT genotypes and IUGR or between COMT Val/Met alleles and IUGR.

Analysis of Single Nucleotide Polymorphisms of COMT Gene in Korean Schizophrenics / 신경정신의학

OBJECTIVES: Catechol-O-methyltransferase (COMT) plays an important role in metabolizing catecholamines, including dopamine. Also, several single-nucleotide polymorphisms (SNPs) of the COMT gene are associated with schizophrenia. Therefore, this study aimed to find the association between COMT gene SNPs and schizophrenia in Koreans. METHODS: Participants were 366 schizophrenia patients and 359 normal controls. To identify the SNPs, we performed genetic analyses in 4 SNP regions, via SNP-ITTM assays. We compared allele, genotype, and haplotype frequencies between the two groups. Moreover, we built subgroups, based on onset age, and compared individual allele and genotype frequencies among these subgroups. RESULTS: In female patients, genotype frequencies showed a significant difference in rs2020917 among the 4 SNPs (p=0.0224), but haplotype frequencies showed no such difference among the 4 SNPs between patients and controls. We noted a significant difference in rs1544325 allele frequencies according to onset age. Also, in female patients, rs1544325 allele and genotype frequencies varied significantly according to onset age. CONCLUSION: This study found no genetic association between the COMT gene's 4 SNPs and schizophrenia in Koreans. However, our findings suggest genetic components for sex-specificity and onset age in Korean schizophrenics.

The Association of COMT Gene Polymorphism and Tourette Syndrome: A Family Based and Case Control Study

OBJECTIVES: Tourette disorder is known to be a disease with a strong genetic trait. There has been some recent research on the relationship between the allelic frequency distribution and Tourette disorder. In Korea, the relationship between the genetic type and the alleles for the COMT gene has been studied in Tourette patients. METHODS: Seventy two patients who were diagnosed with Tourette disorder according to the DSM-IV diagnostic criteria were selected for this study. The diagnosis and clinical features were confirmed by the Yale Global Tic Severity Scale. For the control group, the parents of the patients were chosen. Blood samples were taken from the 289 subjects. DNA was extracted from the blood lymphocytes and PCR was performed for assessing COMT gene. RESULTS: On comparing the Tourette disorder transmitted group and the not-transmitted group, no significant difference was seen between the COMT genetic type and the allelic distribution. CONCLUSION: Even though this result is viewed that there is no relationship between Tourette disorder and the COMT gene, it is difficult to firmly accept this negative result. Follow up studies with a larger patient population or pure subgroups are expected in the future.

Catechol-O-Methyl Transferase Gene Polymorphism and Treatment Response to Clozapine in Refractory Schizophrenia / 대한정신약물학회지

OBJECTIVE: Disturbances in the biogenic amine pathways have been hypothesized to be the biochemical basis of schizophrenia. Catechol-O-methyl transferase (COMT) gene is an important candidate gene due to its function to metabolically inactivating these amines. We investigated the association between 472 G/A (158val/met) and -287 A/G polymorphisms of COMT gene with response to clozapine treatment in refractory schizophrenia. METHODS: One hundred twenty patients of refractory schizophrenia, who were treated with clozapine longer than six months, were participated in this study. We evaluated treatment response on the basis of the difference of re-hospitalization frequency and hospitalization duration before and after the first clozapine administration day. Genotyping of the 472 G/A and -287 A/G polymorphisms was performed by SNapShot method. RESULTS: In 472 G/A polymor-phism, there were no significant differences of the re-hospitalization frequency and the hospitalization duration between the A (-) group and A (+) group, and also no differences among GG, GA, and AA groups. In -287 A/G polymorphism, there were no significant differences between G (-) group and G (+) group. However, we observed significant differences in the re-hospitalization frequency (F=4.38, p=0.015) and in the hospitalization duration (F=3.90, p=0.024) among three genotype groups. CONCLUSION: We found that the treatment response to clozapine was not associated with COMT 472 G/A polymorphism but was positively associated with -287 A/G polymorphism in refractory schizophrenia. However, This association is not strong enough to conclude the association between -287 A/G polymorphism in COMT gene and clozapine response. Further studies with a large sample are required to verify this positive finding more clearly.