• Korean Journal of Biological Psychiatry
• /
• v.14 no.3
• /
• pp.167-176
• /
• 2007

Objectives:A considerable number of pharmacogenetic studies have been performed in recent years to define the association of antipsychotic drug response with dopamine receptor polymorphisms. The purpose of this study was to investigate the relationship between the therapeutic response to antipsychotic drugs and the polymorphisms of the dopamine D2, D3, and D4 receptor genes(DRD2, DRD3 and DRD4, respectively). Methods:We conducted retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia(DSM-IV) who were treated with various antipsychotics(94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, responders and non-responders, by responsiveness to antipsychotic drugs according to a four-point scale used in previous studies; responders included moderate to marked responded patients and non-responders included none to minimal responded patients. We analyzed the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4. Results:Among the total patients of 200, 141(70.5%) were categorized as responders. There were no significant differences in the frequencies of the DRD2, DRD3, and DRD4 alleles and genotypes between responders and non-responders. Conclusion:These results suggest that the Ser311Cys polymorphism in the DRD2, the Ser9Gly polym- orphism in the DRD3, and the exon III 48bp repeat polymorphism in the DRD4 are not associated with the therapeutic response to antipsychotic drugs in Korean schizophrenic patients. A larger prospective study is needed to elucidate the association between antipsychotic response and dopamine receptor gene polymorphism.

• Korean Journal of Biological Psychiatry
• /
• v.2 no.2
• /
• pp.248-251
• /
• 1995

정신분열병의 약물치료에서 중요한 역할을 하는 도파민의 기전은 지금까지 5종류의 수용체들이 발견되고 클론되면서, 새롭고 보다 근본적인 유전학적 접근을 통해 규명될 수 있게 되었다. 특히, 도파민 수용체 D4 (DRD4)는 막단백질의 세포질쪽 세번째굴곡에 48-bp반복 다형성배열을 가지고있다. 이러한 다형성 반복배열이 신호전달에 참여할 가능성이 높은 막단백질의 세포질쪽 굴곡에 있다는것은, 각 개인의 항정신병약물에 대한 민감성의 차이를 포함하여 정신분열병에 대한 개개인의 유전적 차이를 진단할 수 있는 가능성을 제시한다. 이러한 가능성을 검증하기 위하여 주로 손쉽고 빠른 중합효소연쇄반응(PCR)을 사용하여 DRD4의 아형들을 분류하게 되는데, DRD4의 PCR은 그 반복배열과 그 주변배열의 높은 GC함량(78% G+C) 때문에 일반적인 PCR 방법을 변형시켜 사용해야한다. DRD4의 아형을 분류하기 위해 변형된 PCR은 통상적으로 7-deaza dGTP와 10% DMSO를 사용하게된다. 이러한 DRD4 PCR은 대부분의 경우 성공하지만, 항상 모든 시료에서 PCR이 성공되는것은 아니었으며 반복적으로 시도하여 증폭시킬 수 있었다. 이러한 어려움은 대부분이 template DNA에 문제가 있을것으로 의심되며 DNA정제 또는 template DNA를 제한효소로 적절하게 무작위절단하여 성공율을 높일 수 있었다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.19 no.1
• /
• pp.19-27
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.12 no.2
• /
• pp.107-113
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.19 no.1
• /
• pp.60-64
• /
• 2012

Objectives : This study was designed to investigate the association between the dopamine D2 receptor (DRD2) genetic polymorphism [TaqIB (rs17294542) and TaqID (rs1800498)] and patients with schizophrenia. Methods : TaqIB (rs17294542) and TaqID (rs1800498) polymorphism of the DRD2 gene were typed in 100 patients with schizophrenia and 109 normal controls. Results : There were no statistical differences in genotype and allele distribution of TaqIB (rs17294542) and TaqID (rs1800498) genetic polymorphism between patients with schizophrenia and normal controls. Conclusions : These results suggest that the TaqIB (rs17294542) and TaqID (rs1800498) polymorphisms of the DRD2 gene may not be associated with schizophrenia in the Korean population.

• Korean Journal of Biological Psychiatry
• /
• v.2 no.2
• /
• pp.237-247
• /
• 1995

The finding of contrasting results regarding an association between schizophrenia and the Mlul polymorphism site in the dopamine $D_3$ receptor gene prompted us to study the distribution of this palymorphism in Korean schizophrenic patients and controls. The author's approach was case-control study. Schizophrenic patients (n=66) and controls (n=76) were examined by case-control study for distribution of the Mlul polymorphism of the dopamine $D_3$ receptor gene in Korean population to minimize the effect of racial differencies in gene frequencies. The frequency of the allele 1 in schizophrenic patients and controls was 0.66 and 0.76, respectively. There was no significant differencies in the frequency of the allele 1 between schizophrenic patients and controls ($x^2$=3.07, p>.05), and between positive and negative schizophrenic patients ($x^2$=1.02, p>.05). We present here the evidence of a lack of alleic association between the Mlul polymorphism of the dopamine $D_3$ receptor gene and Korean schizophrenic patients and also report no increased homozygosity for the Mlul polymorphism. The assumption that the dopamine $D_3$ receptor gene has a predisposing role in schizophrenia was not supported by this case-control study. Although, the possibility that this gene has a minor gene effects in the etiology of schizophrenia cannot be excluded because of the intrinsic limitations of the methods of analysis and number of subjects in our study.

• Korean Journal of Biological Psychiatry
• /
• v.7 no.2
• /
• pp.152-158
• /
• 2000

Background : No association between schizophrenia and dopamine D4 receptor polymorphisms have been reported. Despite these results, it is premature to exclude the association. It has been suggested that the susceptibility to develop schizophrenia could result from variation at a number loci which may interact or coact with each other. Therefore, we investigated a possible association of combinations of exon III 48bp polymorphism[D4E3] and exon I 12bp polymorphism of the DRD4 gene [D4E1] with schizophrenia. Methods : 207 unrelated Korean schizophrenic patients and 191 healthy controls were recruited. DRD4 genotype was established using the polymerase chain reaction. Statistical analysis consisted of ${\chi}^2$ tests for Hardy-Weinberg proportions and genotypic and allelic frequencies in the patients and control groups. Results : There were no statistically significant differences in the each polymorphisms between schizophrenics and controls. And all genotype frequencies were within Hardy-Weinberg expectations. When the combinations of the polymorphism in schizophrenia and controls were compared, however, there were significant differences at $A1A2^*2/4$ in the distributions of the combinations of D4E1 and D4E3(p<0.01). Conclusions : These findings suggest that the certain combination of D4E1 and D4E3($A1A2^*2/4$) has the protective role to a susceptibility for schizophrenia.

• Korean Journal of Biological Psychiatry
• /
• v.9 no.1
• /
• pp.15-24
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.13 no.4
• /
• pp.299-304
• /
• 2006

Objectives : The purpose of the present study was to investigate whether the TaqI A polymorphism of dopamine receptor D2 gene(DRD2) is associated with Tourette syndrome(TS) and chronic motor tic disorder(CMT) in Korean population. Methods : DRD2 TaqI A RFLP genotyping was carried out with DNA extracted from blood samples of 75 patients with tic disorders(47 with TS and 28 with CMT) and 90 healthy subjects. Genotype and allelic frequencies for the DRD2 gene polymorphisms of the tic disorder group as a whole were compared to those of the control group. Separating the TS group, thereafter, the frequency of genotypes and alleles were compared to those of the controls. Results : The results demonstrated that genotype and allele distributions for the DRD2 gene polymorphism in the tic disorder as a whole, TS, and control groups were not significantly different. Conclusion : No association was found for DRD2 gene, TS and CMT. The data suggest that DRD2 gene may not be a useful marker for the prediction of the susceptibility of tic disorder.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.12 no.2
• /
• pp.179-191
• /
• 2001

Objectives：This study evaluated the association between behavioral characteristics and polymorphisms in DAT1, DRD2, DRD3, and DRD4 genes. Methods：The subjects were 114 neonates, who were born by normal spontaneous vaginal delivery and had no physical problems. The behavioral characteristics were evaluated using Neonatal Behavioral Assessment Scale(NBAS) at $17.8{\pm}7.0$ hours after their birth to minimize environmental influences, and cord blood was used to analyze the gene polymorphisms. Results：In comparison to DAT1 gene 10/10 genotype group(N=93), other genotype group(N=19) showed significantly high NBAS scores on social-interaction, state organization, and state regulation. DRD2 gene Ser311/Cys311, TaqI A, and TaqI B polymorphisms showed no significant differences on NBAS scores when they were grouped by genotypes. DRD3 gene polymorphism and DRD4 gene promotor polymorphism showed no significant difference on NBAS scores when they were grouped by genotypes. In comparison to the short repeats(N=102), long repeats(N=10) in DRD4 gene showed significantly high habituation score of NBAS. Conclusion：These results suggest that the genetic effects of the neonatal behavioral characteristics may be mediated via DAT1 and DRD4 genes.