• Journal of Gastric Cancer
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• 제6권3호
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• pp.132-138
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• 2006

목적: 도파민은 중추신경전달물질이지만 위장관에서 도파민수용체와 결합하여 점막상피세포 증식, 상피세포의 보호, 위암 세포증식과 관련이 있는 것으로 알려져 있다. 본 연구에서는 위암에서 기원한 세포주를 이용하여 도파민과 각각의 도파민 수용체가 위암 세포 증식과 억제에 작용하는 역할에 대해 알아보았다. 대상 및 방법: 위암세포기원에서 각각 유래한 세포주인 SNU601과 KCU-C2를 이용하여 RNA 추출 후 RT-PCR 시행 후 도파민수용체 D1, D2L과 D2S 각각에 대한 primer로 PCR을 시행하여 수용체 유전자의 상대적인 발현정도를 측정하였다. 도파민과 Dl 수용체의 대항제인 SCH 23390과 D2 수용체 대항제인 raclopride를 사용하여 약물처리에 따른 위암세포주에서 세포 증식에 대한 분석을 하였다. 결과: KCU-C2 세포주에서 D1과 D2L과 D2S 유전자 mRNA의 상대적인 발현정도는 모두 높은 발현을 보였지만, SNU 601 세포주에는 mRNA의 발현이 모두 낮은 수준이었으며, 특히 D2L mRNA는 발현되고 있지 않았다. 약물처리에 따른 위암세포주에서 세포증식에 대한 분석에서는 D1과 D2S 수용체를 통한 도파민의 신호는 세포의 증식을 억제하였고 D2L 수용체를 통한 도파민의 신호는 세포의 증식을 유도하였다. 결론: 본 연구를 통해 도파민이 위암의 세포증식과 억제에 관여하며, 도파민의 이러한 효과는 도파민의 신호가 어느 수용체를 통해 전달되었느냐에 따라 위암세포의 증식과 억제가 이루어짐을 알 수 있었다.

• 생물정신의학
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• 제2권1호
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• pp.57-62
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• 1995

항정신병 약물인 clozapine이 주로 작용하는 도파민 수용체로 알려진 도파민 $D_4$ 수용체는 각각 50 염기쌍에 해당하는 크기의 차이가 있음이 알려져 PCR을 이용해 정신분열증 환자와 정상대조군을 대상으로 도파민 $D_4$ 수용체 유전자의 대립형질 분포를 알아보았다. 정신분열증 환자군과 대조군 모두에 있어 여섯종류의 대립형질의 관찰되었으며 정신분열증 환자에서 네번 반복형태의 대립형질이 수적으로 더 많이 관찰되었지만 통계적으로 유의한 차이는 없었으며 정신분열증과 관련된 도파민 $D_4$ 수용체 유전자의 대립형질은 확인되지 않았다. 그러나 보다 객관적인 정보를 얻기 위해서 clozapine에 대한 반응에 따라 정신분열증 환자의 아형을 분류하고 그 아형에 따른 도파민 $D_4$ 수용체 유전자 대립형질분포의 차이에 관한검증이 필요하며, 나아가 도파민 $D_4$ 수용체 유전자의 발현에 있어 정신분열증 환자와 정상인에 차이가 있는지 여부를 밝히는 추적연구가 필요할 것으로 사료된다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제19권1호
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• pp.19-27
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• 2008

Objectives : The aim of this study was to examine the association of attention-deficit hyperactivity disorder (ADHD) in Korean populations with functional polymorphisms of six genes dopamine receptors (Ser311/Cys311 polymorphism, Taq1 A polymorphism, and Taq1 B polymorphism in DRD2, BalI polymorphism in DRD3, and promoter -521 C/T polymorphism and exon III 48 bp repeat polymorphism in DRD4) and one gene in dopamine transporter (DAT1). Methods : Participants were 58 children with ADHD and 110 control children. The genotypes were determined by PCR. Results : There was a statistically significant difference in genotype frequency of -521 C/T polymorphism within the promoter region of the DRD4 between two groups. Furthermore, in the male group, both genotype and allele frequencies showed statistically significant differences. Conclusion : Findings of the study indicate that -521 C/T polymorphism in promoter region of DRD4 appears to be a possible candidate gene for ADHD in Korean population.

• 생물정신의학
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• 제12권2호
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• pp.107-113
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• 2005

Purpose:In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine $D_2$ receptor polymorphism in schizophrenic patients. Methods:The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine $D_2$ receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). Results:The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (${\chi}^2$(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. Conclusions:The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.

• 생물정신의학
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• 제7권2호
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• pp.159-163
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• 2000

Background : Dopamine receptors are strong candidates for involvement in schizophrenia and are target of a wide variety of antipsychotics. Dopamine $D_5$ receptor(DRD5) gene polymorphisms may be associated with various treatment response. The purpose of our study was define to what significance can be held as a predictor of treatment response in this polymorphism. Method : The total number of 116 Korean chronic schizophrenic patients was assessed after 48 weeks treatment. The Positive and Negative Syndrome Scale(PANSS) was rated for the clinical response to various antipsychotics. With the use of polymerase chain reaction amplification, we assessed this dopamine $D_5$ receptor polymorphism in schizophrenic patients who had been treated with antipsychotics, and related genotype with treatment response, to test the hypothesis that DRD5 polymorphism may lead to varying response to antipsychotics. Result : DRD5 polymorphism was not associated with treatment response to a variety of antipsychotics in chronic schizophrenic patients. Conclusion : Genetic variation of $D_5$ receptors do not predict treatment response to antispychotics.

• 생물정신의학
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• 제8권1호
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• pp.106-110
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• 2001

Background : Dopamine receptors have been regarded as a strong candidate involved in etiology of schizophrenia and a target for various antipsychotic drugs. The purpose of our study was to investigate whether dopamine $D_1$ receptor(DRD1) gene polymorphisms would predict the treatment response to antipsychotics in schizophrenia. Method : One hundred thirty-four schizophrenic patients, who met DSM-IV criteria for schizophrenia were entered into a 48 -week study. The psychopathology of the patients was assessed at baseline, 12th, 24th 48th weeks of treatment by PANSS. Responders were defined by a 20% of the reduction in total PANSS score at end point. The genomic DNA fragment corresponding to nucleotides of dopamine $D_1$ receptor gene was amplified by polymerase chain reaction(PCR). Result: Neither allelic frequencies nor genotypes for dopamine $D_1$ receptor differed significantly between responders and non-responders. Also, there was no difference of changes of PANSS scores among three genotype groups of the dopamine $D_1$ receptor. Conclusion : Allelic variation in the dopamine $D_1$ gene is not associated with individual differences in antipsychotic response.

• 생물정신의학
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• 제8권2호
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• pp.246-250
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• 2001

The dopamine D4 receptor gene has a hypervariable segment in the coding region characterized by a varying number of 48bp repeats in exon III of the gene. Varying the numbers of repeated segments may change the length, structure, and function of the receptor, which makes this gene a possible candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. We evaluated the dopamine D4 receptor genotype in male alcoholics and normal controls. All alcoholics and controls were unrelated and from the Korean population. Genotype and allele frequencies in 67 alcoholics were compared to 67 controls who were free of alcohol abuse, substance abuse, and major mental illness. No association was found between the dopamine D4 receptor allele and alcoholism. This result indicate that there is no association of the dopamine D4 receptor with alcoholism in Korean. Further systemized investigation to determine the role of dopamine D4 receptor gene in alcoholism with a larger sample size will be required.

• 생물정신의학
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• 제2권2호
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• pp.237-247
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• 1995

도파민 $D_3$ 수용체 유전자와 정신분열증 병인과의 연관성을 밝히고자 본 연구에서는 한국에서의 정신분열증환자 66명과 정상대조군 76명에서 다형성의 분포를 PCR을 이용하여 환자대조연구 방법으로 조사하였다. 정신분열증환자에서 대립유전자 1의 빈도는 0.66이었고, 정상 대조군에서는 0.76이었다. 즉, 두군간에 대립유전자 1의 빈도에는 유의한 차이가 없었고, 양성 및 음성 증상군 척도평가에 의한 정신분열증의 양성아형과 음성아형간에도 유의한 차이가 없었다. 정신분열증 환지에서는 전체 66명중 동형 접합체가 43명으로 65.1%. 이형 접합체는 23명으로 34.9%였다. 정상 대조군에서는 전체 76명중 동형접합체가 54명으로 71.1%. 이형접합체는 28.9%였다. 이러한 결과는 이전의 정신분열증과 도파민 $D_3$ 수용체 유전자간의 연관관계를 연구한 외국의 연구결과와 일치하며 도파민 $D_3$ 수용체 유전자가 정신분열증 병인의 원인일 것이라는 가설을 뒷받침하지는 못하였다.

• 생물정신의학
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• 제9권1호
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• pp.15-24
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• 2002

Even though alcoholism is a multi-factorial psychiatric disorder, it is reasonable to suppose that genetic factors play a substantial role in the manifestation of this disorder. Because alcohol is the reinforcing substance which manifests its effects through activation of the mesolimbic dopaminergic reward pathway of the brain, the gene encoding dopamine receptor subtypes can be a major natural candidate gene. Since 1990, many association studies have identified strong evidence implicating the dopamine D2 receptor(DRD2) gene in alcoholism, specifically TaqI A minor(A1) allele. Association studies have also been conducted on other dopamine receptor(DRD3 & DRD4) polymorphisms but the results have yet to be confirmed. Through a number of other approaches, each dopamine receptor gene has been investigated in association with different phenotypes in alcoholism, but further researches will be needed. In conclusion, studies in the past decade have shown that the TaqI A1 allele of the DRD2 gene is associated with alcoholism in various subject groups. Other dopamine receptor genes have since been added to the list but yet to be identified. Thus, the knowledge of these genes and their functional significance will enhance the understanding of the underlying biological mechanisms of alcoholism. Furthermore, it could lead to more helpful prevention and treatment approaches to alcoholism.

• 생물정신의학
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• 제4권2호
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• pp.218-224
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• 1997

The results regarding an association between the polymorphism sites in the dopamine $D_1$ receptor gene and schizophrenia compelled us to study the distribution of the polymorphism in Korean schizophrenia and controls. Eighty-eight schizophrenic patients and normal controls were examined by case-control study for distribution of the polymorphism of the dopamine $D_1$ receptor gene in Korean popualtion to minimize the effect of racial differencies in gene frequencies. The frequencies of the $B_1$ and $B_2$ in schizophrenic patients were 0.11 and 9.89, respectively. And 0.10 and 0.90 in normal control. Ther was no significant differences in the frequencies in the allele $B_1$ and $B_2$between schizophrenic patients and normal controls. The author present here the evidence of a lack of alleic association between the polymorphism of the dopamine $D_1$ receptor gene and Korean schizophrenic patients. The assumption that the dopamine $D_1$ receptor gene has a genetic role in the development of schizophrenia was not suppoorted by this case-control study.