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

• Environmental Mutagens and Carcinogens
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• v.23 no.1
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• pp.7-10
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• 2003

Hypertension is characterized by multiple genetic and environmental factors. To establish the genetic basis of hypertension in Koreans, we investigated the genetic variations of dopamine D3 receptor (DRD3) gene in the Korean patients with hypertension and normotensive controls. There were no significant differences in the genotype and allele frequencies of Bal I RFLP in the DRD3 gene between two groups, respectively (P > 0.05). Our finding shows lack of association between a genetic marker of DRD3 gene and hypertension, suggesting that the genetic variation of DRD3 gene does not playa major role in the determination of hypertension in Korean population. Further studies in other ethnic groups will be required.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.19 no.1
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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.

• Korean Journal of Biological Psychiatry
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• v.9 no.1
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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.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.116-122
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• 2001

Objectives : Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the $D_3$ receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response in chronic schizophrenic patients. Methods : Therapeutic response for 116 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). Results : Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. Conclusion : A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.

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

• Environmental Analysis Health and Toxicology
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• v.18 no.4
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• pp.243-247
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• 2003

고혈압은 다양한 유전적 요인과 환경적 요인들이 상호작용하여 발병하는 질환으로, 기존의 연구에서 dopamine D3 receptor(DRD3)와 고혈압과의 관련성에 관한 보고들이 있었다. 이에, 본 연구에서는 DRD3 유전자에 존재하는 Bail제한절편길이 다형성이 한국인 집단에서 고혈압과 어떠한 관련성이 있는 지를 조사하였다. 환자-대조군 연구를 수행한 결과 이 유전자에 존재하는 다형성은 한국인 집단에서 고혈압과 유의한 관련성을 나타내지 않았다. 그러나, 이 다형성을 구성하는 대립 유전자의 빈도를 여러 민족집단의 결과들과 비교했을 때, 흑인 집단과 유의한 차이를 나타내었다. 따라서, 이러한 결과는 DRD3유전자에 존재하는 다형성이 고혈압과의 관련성을 나타내는 지를 정확하게 이해하기 위해서는 혹인 집단을 비롯한 다른 민족집단들을 대상으로 하여 광범위한 연구를 수행할 필요가 있을 것으로 생각된다.

• Korean Journal of Biological Psychiatry
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• v.14 no.3
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• pp.167-176
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• 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
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• v.20 no.3
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• pp.91-96
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• 2013

Objectives The aim of this study is to evaluate the association between rs6280 and rs905568 genetic polymorphism of DRD3 gene and the treatment response of amisulpride. Methods After six weeks treatment of amisulpride, 125 schizophrenia patients were interviewed based on the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression-Severity (CGI-S). The genotyping for rs6280 and rs905568 was performed using TaqMan single nucleotide polymorphism (SNP) genotyping assay. Results There was no significant difference in the frequency of genotype and allele of rs6280 between the responders and non-responders based on the total, positive, and general score of PANSS and CGI-S score. However, there was a significant association between this SNP and treatment response in the negative score of PANSS (${\chi}^2=5.23$, p = 0.022). There was no significant association between rs905568 and the response in positive, negative, general, and total PANSS score and CGI-S score. Conclusions This is the first positive association study between DRD3 gene and the treatment response of negative symptoms to amisulpride in Korean schizophrenia patients. A larger scale research on more SNP of the DRD3 gene will make a progress in the study of pharmacogenetics on the treatment response of the amisulpride.

• Korean Journal of Biological Psychiatry
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• v.13 no.3
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• pp.178-190
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• 2006

Objectives : We investigated the relationship of the alcohol withdrawal symptoms with genetic polymorphism among alcohol dependence patients. Method : The measuring instruments used in this study were the Clinical Institute Withdrawal Assessment for Alcohol(CIWA-Ar). We analyzed DRD2 TaqI A polymorphism, dopamine transporter(DAT 1) polymorphism, and catechol-O-methyltransferase(COMT) polymorphism in 108 male alcoholics and 76 healthy controls. Results : The major findings was as follows. No significant differences for genotype distribution or allele frequency were revealed comparing controls and alcoholic patients. DRD2 Taq I : The subscale score of auditory hallucination among CIWA-Ar scale in homozygote was significantly higher than in heterozygote(OR=1.34). The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. DAT1 : In the subject without DAT-9 gene allele, it was significantly higher of the subscale score of sweating, anxiety among CIWA-Ar scale than in the subject with DAT-9 gene allele. And The total score of CIWA-Ar scale in the subject without DAT-9 gene allele was significantly higher than in the subject with DAT-9 gene allele. COMT : The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. Conclusion : Our results suggest the relationship between specific genetic factors and the withdrawal symptoms of alcohol dependent patients. As the candidate gene of the severity of alcohol withdrawal syndrome, DRD2 Taq1 gene was recommended.