• 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.8-14
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• 2002

Patients with attention deficit hyperactivity disorder(ADHD) have symptoms of inattention, hyperactivity, impulsivity. Symptoms of ADHD are responsive to medications such as methylphenidate, dextroamphetamine, pemoline, and bupropion. The functional change of the dopamine transporter is related to the therapeutic effect of these drugs. This can be one reason for the dopamine transporter to be emphasized in the research field of ADHD. ADHD has a genetic tendency. Since dopamine transporter gene(DAT1) knock out mice were reported to be several times more active than normal mice in a novel situation, lights has been shed on DAT1 as a candidate gene for ADHD. Though there have been several studies which reported an association between DAT1 and ADHD, the association between DAT1 and ADHD is not conclusive. Since Vandenbergh reported the DAT1 polymorphism with variable number of tandem repeats(VNTR), and the racial differences in allelic frequencies of the DAT1, wide ethnic variation in the distribution of the DAT1 polymorphism had been confirmed. Wide ethnic variation in the distribution of the DAT1 suggested that there might be ethnic difference in the association between DAT1 and ADHD. Before applying previous findings to Koreans, verification might be needed for Korean patients with ADHD.

• Korean Journal of Biological Psychiatry
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• v.11 no.2
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• pp.165-172
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• 2004

Objective:Although polymorphism of dopamine transporter gene(DAT1) has been considered to be implicated in the pathogenesis of social phobia, previous investigations have been inconsistent and controversial. The authors investigated the relationship between DAT1 polymorphism and social phobia in Koreans. Methods:DAT1 and alleles of fifty subjects who met DSM-IV criterion of social phobia, and those of age- & sex- matched fifty normal controls in Korea were compared. Additionally, patients were grouped into generalized(33) and nongeneralized(17) types and DAT1 polymorphism was compared with that of age- & sex- matched controls. DAT1 with variable number of tandem repeats(VNTR) were determined by using polymerase chain reaction. To compare the distribution of the DAT1 polymorphism between different groups, Fisher's exact test was used. Results:There were no significant differences in either genotypic(p=0.451) or allelic(p=0.452) distributions between the social phobia patients and the controls. There also were no differences in genotypic distribution between subtypes of social phobia patients and the controls. Conclusion:We couldn't find any association between DAT1 polymorphism and social phobia. Further studies including larger number of samples and diverse clinical variables should be conducted to elucidate the present findings.

• 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.

• Korean Journal of Biological Psychiatry
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• v.14 no.1
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• pp.55-60
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• 2007

Objectives : There have been many association studies of panic disorder. However, studies about the dopaminergic function in panic disorder have been few. This study was aimed to examine the possible association of dopamine transporter gene(DAT1) polymorphism and panic disorder in Korean population. Methods : Ninety-eight patients with panic disorder(43 male(46.9%), mean age $42.13{\pm}10.88$ years) and one hundred and thirteen comparison subjects(67 male(40.7%), mean age $33.14{\pm}8.55$ years) were tested for DAT1 polymorphism. Genotypes of DAT1 with variable number of tandem repeats(VNTR) were determined using polymerase chain reaction. The differences of allelic frequency and genotype frequency distribution between patient and the control group were tested with Fisher-Freeman-Halton test. Results : There was association between DAT1 polymorphism and panic disorder(allele : p<0.03, genotype : p<0.05). The frequency of 10/10 homozygotes of DAT1 was significantly higher in control group(${\chi}^2$=4.452, df=1, p=0.035). Conclusion : These results in our Korean samples suggest that DAT1 polymorphism might be associated with the vulnerability of panic disorder. Possible association of dopaminergic genes and panic disorder should be investigated with future studies using larger and different population.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.239-245
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• 2001

Objective : Dopamine transporter is member of family of Na/Cl dependent neurotransmitter transporter, 12 transmembrane domain, that has high substrate specificity, affinity. It is related with dopamine reuptake in presynaptic vesicle. DAT has a VNTR in its 3'-untranslated region(UTR). 3'-UTR VNTR polymorphism is related with modification of dopamine transmission. The association between with VNTR polymorphism and neuropsychiatric disorders such as alcohol dependence, and low activity ALDH has been studied, but their relationship is unclear. We study about association of 3'-UTR VNTR of DAT gene and G2319A and alcohol dependence. Method : Group of Korean subjects were studied with alcohol dependence(n=49 male) compared to mentally healthy controls(n=53 male). The peripheral blood sample was acquired, and Polymerase Chain Reaction(PCR) amplification, MspI procedure was done. Result : There was a significant difference between alcohol dependence group and normal control(genotype frequency p<0.05, allele frequency p<0.05) Allele A frequency and genotype(GG, GA) frequency was a significant difference between alcohol dependence group and normal control(p<0.05). Conclusion : Our study showed that genetic polymorphism of DAT1 G2319A had relation with alcohol dependence.

• Sleep Medicine and Psychophysiology
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• v.15 no.1
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• pp.39-43
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• 2008

Objectives: The pathophysiology of restless legs syndrome (RLS) is not obvious, but many promising theories involve dopaminergic deficiency and genetic causes. The RLS is presumed to occur more frequently among schizophrenic patients who take antipsychotics, most of which blocks the dopamine receptors. This study aimed to investigate whether dopamine transporter gene (DAT1) 40 base pair (bp) variable number of tandem repeat (VNTR) polymorphism is associated with the antipsychotic-induced RLS in schizophrenia. Methods: We determined the diagnosis of RLS among the 190 Korean schizophrenic patients by the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG). Genotyping was performed for the 40bp VNTR in DAT1 gene using polymerase chain reaction. Results: We separated the schizophrenic patients into 44 patients with RLS and 146 patients without RLS. The genotype and allele frequencies did not differ significantly between two groups. Conclusions: These results suggest that DAT1 gene 40bp VNTR is not associated with the antipsychotic-induced RLS in schizophrenia. To confirm these results, larger-scale association study is needed in the future.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.16 no.2
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• pp.199-210
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• 2005

Objective : Attention deficit hyperactivity disorder(ADHD) affects $5-10\%$ of children in Korea, with more boys and girls being diagnosed. Despite seriousness of ADHD, little is known about its causes. From the current genetic epidemiologic studies, ADHD is known as a heritable disorder. Till now, however, there have been very few genetic studies about ADHD in Korea. The aim of the this study is to examine the association between dopamine transporter gone type 1 and ADHD using case-control design in Korean ADHD probands and normal controls. Materials and Method : Child Psychiatric Genetic research team in Seoul National University Hospital, Clinical Research Institute recruited the ADHD probands using clinical interview/observation, diverse rating scales, and neuropsychological tests. For eliminating phenocopy or ADHD, diagnosis of ADHD was based upon clinical data, psychometric data, and parent/teacher reports. Total 85 ADHD-probands were recruited as final study subjects and independent 100 normal adults participated in this study as control group. For all the ADHD probands, and controls, the 3'-UTR-VNTR polymorphism of DAT1 was analyzed. Based on the DAT1 allele and genotype informations, Chi-square test based on case-control design was performed. Results : As for genetic study, total of 85 probands and 100 controls were included for the genetic analysis. Four different alleles, 350bp (7repeat), 440bp (9repeat), 480bp (10repeat) and 520bp (11repeat) were found in DAT1 gene of study subjects. In case-control analysis, ADHD probands and parents have significantly more 9 repeat allele and 9/10 genotype. Also, The probands with 9repeat allele have more commission errors in ADS. Conclusion : The positive association between ADHD and DAT1 gene was replicated in this report like other previous results for caucasian children and Korean children with ADHD. There are ongoing studies on other candidate genes such as DRD4 and DRD5 and it would be required to explore the association of these candidate genes in Korean children with ADHD. These ongoing genetic research will contribute to the understanding of heterogenous genetic and environmental etiologies of ADHD phenotype, which will lead to the development of more comprehensive treatment and preventive interventions for ADHD.

• 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.