OBJECTIVES: In the present study, we investigate the association between homozygosity of the 4-repeat allele (4/4) at the DRD4 and the response to the treatment with MPH in Korean children with ADHD. METHODS: The present study included 71 children with ADHD (8.231.78 years) from two children's psychiatric clinics in South Korea. All drug-naive children with ADHD were treated with MPH for about 8 weeks. The subjects who showed improvement of over 50% compared with the baseline ARS score after 8 weeks of treatment were termed as the 'good response' group. The subjects who showed an improvement of less than 50% were considered as the 'poor response' group. After genotyping for DRD4 were performed, we investigated correlation between homozygosity for 4-repeat allele at DRD4 and the response to MPH treatment. RESULTS: We found that while 79.5% (31/39) of the subjects with homozygosity of 4-repeat allele at DRD4 showed good response to MPH treatment, 68.8% (22/32) of the subjects without homozygosity of 4-repeat allele at DRD4 showed poor response to MPH treatment according to ARS scores assessed by their parents (chi2=16.762, df=1, p<0.01). We also found that while 61.5% (24/39) of the subjects with homozygosity of4-repeat allele at DRD4 showed good response to MPH treatment, 87.5% (28/32) of the subjects without homozygosity of the 4-repeat allele at DRD4 showed poor response to MPH treatment according to ARS scores assessed by their teachers (chi2=17.698, df=1, p<0.01). CONCLUSION: Our findings support an association between the homozygosity of 4-repeat allele and a good response to MPH in ADHD of Koreans.
Alleles ; Child* ; Dopamine* ; Humans ; Korea ; Methylphenidate* ; Parents ; Receptors, Dopamine D4*

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 co-act with each other. Therefore, we investigated a possible assoication of combinations of exon III 48bp polymorphism [D4E3] and exon I 12bp polymorphism of the DRD4 gene [D4E1] with schizophrenia. METHOD: 207 unrelated Korean schizophrenic patients and 191 healthy controls wee recruited. DRD4 genotype was established using the polymerase chain reaction. Statistical analysis consisted of chi2 tests for Hardy-Weinberg proportions and genotypic and allelic frequencies in the patients and control groups. RESULT: 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). CONCLUSION: These findings suggest that the certain combination of D4E1 and D4E3 (A1A2*2/4) has the protective role to a susceptibility for schizophrenia.
Dopamine* ; Exons ; Genotype ; Humans ; Polymerase Chain Reaction ; Receptors, Dopamine D4 ; Schizophrenia

OBJECTIVETo study polymorphisms of dopamine D4 receptor (DRD4) in children with primary nocturnal enuresis (PNE) and explore the relationship between DRD4 gene polymorphisms and PNE.

METHODSGenomic DNA was isolated from leukocytes in 86 unrelated children with PNE and in 100 healthy unrelated children (controls). Polymorphisms of DRD4-1240L/S, -616C/G and -521C/T were genotyped by allele-specific primer PCR.

RESULTSThere were significant differences in allele frequencies (x2=8.13, P<0.05) and genotypes frequencies (x2=6.23, P<0.05) of DRD4-616C/G between PNE patients and healthy controls. The frequency of haplotype LCT consisting of 3 function polymorphic sites DRD4-1240L/S, -616C/G and -521C/T in PNE patients was statistically higher than that in healthy controls (x2=5.88, P<0.05).

CONCLUSIONSThe change of C to G of DRD4-616 may affect the induction and transcription of DRD4 gene. The haplotype LCT consisting of 3 function polymorphic sites DRD4-1240L/S, -616C/G and -521C/T may synergistically inhibit the transcription activity of DRD4 gene. This might lead to a reduction of DRD4 protein expression and cause nocturnal enuresis.

Adolescent ; Child ; Female ; Genotype ; Haplotypes ; Humans ; Male ; Nocturnal Enuresis ; genetics ; Polymorphism, Genetic ; Receptors, Dopamine D4 ; genetics

OBJECTIVE: The aim of this study was to evaluate the association between a variable number of tandem repeats polymorphism at the dopamine D4 receptor gene (DRD4) and the performance of children with attention deficit hyperactivity disorder (ADHD) in a continuous performance test (CPT). METHODS: This study included 72 ADHD children (mean age=9.39+/-2.05 years) who were recruited from one child psychiatric clinic. The omission errors, commission errors, reaction time and reaction standardization in the CPT were computed. The number of 48-base pairs tandem repeats in the exon III of DRD4 was analyzed in a blind manner. RESULTS: The homozygosity of the 4-repeat allele at DRD4 was significantly associated with fewer commission errors (t=2.364, df=28.685, p=0.025) and standard deviation of reaction time (t=2.351, df=24.648, p=0.027) even after adjusting for age. The results of analyses of CPT measured values among three groups showed that the group with higher frequency of the 4-repeat allele showed a lower mean score of commission errors (F=4.268, df=2, p=0.018). CONCLUSION: These results suggest a protective role of 4-repeat allele of the DRD4 polymorphisms on commission errors in the CPT in children with ADHD.
Alleles ; Attention Deficit Disorder with Hyperactivity ; Child ; Dopamine ; Exons ; Humans ; Minisatellite Repeats ; Reaction Time ; Receptors, Dopamine D4 ; Tandem Repeat Sequences

Human personality traits have a considerable genetic component. Cloninger et al. were the first to postulate that certain personality traits, such as novelty seeking, are related to the dopamine neurotransmitter system. In this study, we investigated the associations between dopamine receptor D4 (DRD4) exon III and dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose personality traits were assessed with the Temperament and Character Inventory (TCI). There were no significant differences between scores of TCI temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no significant association with any of the temperament subscales of the TCI. These data suggest that DRD4 and DAT1 gene polymorphism may not associated with personality traits in a Korean population.
Temperament ; Receptors, Dopamine D4/*genetics ; *Polymorphism, Genetic ; Personality/*genetics ; Male ; Korea ; Humans ; Female ; Dopamine Plasma Membrane Transport Proteins/*genetics ; Adult

The dopamine D4 receptor gene has a hypervariable segment in the coding region charcterized 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 dopamin D4 recepto 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.
Alcoholics ; Alcoholism* ; Alleles ; Clinical Coding ; Dopamine* ; Exons ; Gene Frequency ; Genotype ; Humans ; Male ; Receptors, Dopamine D4* ; Sample Size ; Substance-Related Disorders

BACKGROUND: Recent research demonstrates a strong association between smoking-related behaviors and genetic variation. We investigated the clinical features and genetic effects of dopamine receptors and a serotonin transporter on smoking cessation in Koreans. METHODS: Smokers (n=51) wanting to quit smoking were included as the study population. They were genotyped for polymorphisms in dopamine D2 receptor (DRD2) (TaqI and -141C), dopamine D4 receptor (DRD4), and a serotonin transporter (5-HTT). We defined abstinence as stopping smoking at six months after enrollment. RESULTS: Eighteen patients (35.3%) stopped smoking at six months. The abstinence group had a higher rate of alcohol use whereas the non-abstinence group had more coughing. However, there were no significant differences in average smoking rate, starting age of smoking, gender, nicotine dependence, and forced expiratory volume in one second between the two groups. As for the genes in the dopamine pathway, the polymorphisms of DRD2 TaqI (A1 allele) and DRD2 -141C (Ins C allele) were not genotypically different between the two groups (P=0.245 and 0.409, respectively). The genetic variation in the DRD4 variable number of tandem repeats (VNTR) also showed a similar distribution in the two groups. Regarding the polymorphisms of 5-HTT, there was no difference in the long allele between the two groups (P=0.852). CONCLUSIONS: This study suggests that the genetic variations of DRD2 TaqI, DRD2 -141C, DRD4 VNTR, and 5-HTT might have little influence on smoking cessation in Korean smokers.
Alleles ; Cough ; DNA ; Dopamine ; Forced Expiratory Volume ; Genetic Variation ; Humans ; Minisatellite Repeats ; Polymorphism, Genetic ; Receptors, Dopamine ; Receptors, Dopamine D2 ; Receptors, Dopamine D4 ; Serotonin Plasma Membrane Transport Proteins ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Use Disorder

OBJECTIVEAttention deficit hyperactivity disorder (ADHD) is one of the most common behavior disorders in childhood and adolescent. The etiology of ADHD is unknown. The aim of this study was to investigate the relationship between each of the 14 polymorphisms in the five candidate genes and ADHD, and between the combination of some polymorphisms in those genes and ADHD, in attempting to examine whether combinations of genotypes would confer a significant susceptibility to ADHD.

METHODSOne hundred and thirty-nine children with ADHD and one hundred and nineteen normal children were enrolled. Eight single nucleotide polymorphisms (SNP) of three candidate genes were examined with PCR and RFLP techniques. 48 bp VNTR in DRD4 gene was examined with PCR, nondenaturing polyacrylamide gel electrophoresis and silver staining. Five microsatellites (MS) of three candidate genes were examined with genotyping. The relationship between the combinations of 12 polymorphisms and ADHD was examined with logistic regression analysis.

RESULTS1.The frequency of 1065T/1065T genotype and the 1065T allele were significantly higher in ADHD children than that in normal controls (P<0.05). The frequency of -48G/-48G genotype of the A-48G polymorphism of DRD1 gene was significantly lower in ADHD children than that in normal controls (P<0.05). 2. A specific combination of three polymorphisms in the two genes showing an association with ADHD gave a prediction level of 77.5%.

CONCLUSIONSThe T1065G polymorphism in the SNAP-25 may be associated with ADHD. The 1065T/1065T genotype and the 1065T allele may be a risk factor for ADHD. The A-48G polymorphism of DRDI may be associated with ADHD. The -48G/-48G genotype may be a protective factor for ADHD. The specific combination of three sites of SNP in SNAP-25 gene and DRDI gene is found and shows an association with ADHD in 12 polymorphisms of the five candidate genes on glutamatergic/dopaminergic pathway.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; genetics ; Child ; Female ; Humans ; Logistic Models ; Male ; Minisatellite Repeats ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D3 ; genetics ; Receptors, Dopamine D4 ; genetics ; Receptors, Dopamine D5 ; genetics ; Receptors, N-Methyl-D-Aspartate ; genetics ; Synaptosomal-Associated Protein 25 ; genetics

OBJECTIVES: The aim of this study is to explore the association among DRD4 polymorphism, temperament and alcohol drinking behavior of Koreans in their early adulthood. METHOD: Participants were 172 healthy Korean adults (mean age 28.1 +/- 0.8). Their temperament was assessed with the Temperament and Character Inventory (TCI) and their alcohol drinking behavior were evaluated with a self-reported questionnaire including the CAGE and the Korean version of Alcohol Use Disorder Identification Test (AUDIT-K). DRD4 exon III 48 base pair variable number of tandem repeats (VNTR) was genotyped by PCR. RESULTS: No significant association was found between DRD4 polymorphism and TCI temperament dimension (novelty seeking, harm avoidance, reward dependence, and persistence) as well as alcohol drinking behavior scales. However, novelty seeking was significantly associated with alcohol drinking behavior. The higher level of novelty seeking was associated with the higher severity index of drinking (B = -0.225, p < 0.001) and problematic alcohol use on the CAGE and AUDIT-K [Odds Ratio (OR) = 1.111, 95% Confidence Interval (CI) 1.021-1.209, p = 0.015, OR = 1.087, 95% CI 1.009-1.170, p = 0.028]. CONCLUSION: In our study, while there is no significant association of DRD4 polymorphism with temperament and alcohol drinking behavior, novelty seeking affects problematic alcohol use. Results suggest that novelty seeking may play an important role in problematic alcohol use in young Korean adults.
Adult ; Alcohol Drinking ; Base Pairing ; Dopamine ; Drinking ; Exons ; Humans ; Minisatellite Repeats ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, Dopamine D4 ; Reward ; Temperament ; Weights and Measures ; Surveys and Questionnaires

OBJECTIVES: The studies on the genetic risk factors of the children of alcoholics (COAs) are still in an early stage. The A 1 allele of the dopamine receptor 2 gene (DRD2) may be associated with the negative affect and positive alcohol expectancy of the COAs. In addition, several researchers reported that COAs might be associated with the GABAA receptor beta subunit gene (GABRB3) and serotonin transporter gene (5-HTTLPR). In this study, we investigated the association of polymorphism of the DRD2, Dopamine D4 receptor gene (DRD4), GABRB3, 5-HTTLPR with COAs to examine the genetic risk factors of COAs. METHODS: Twenty-two COAs and 23 control children (children of non-Alcoholics ; Non-COAs) were included for the genetic study. All COAs aged 6 to 18 were recruited and selected from families of alcoholic patients in alcohol clinics of three university and mental hospital. Alcoholism of parents was classified as type I (non-antisocial, late onset) and type II (antisocial, early onset) by Cloninger's classification. The genotyping of the DRD2, DRD4, GABRB3, 5-HTTLPR was carried out. Chi-square method was used for evaluating the associations between genetic polymorphism and the COAs. RESULTS: The frequency of A1+ allele of DRD2 in COAs were significantly higher than Non-COAs (Chi-square=4.45, df=1, p=0.035). Significant association between the genotype of DRD4 and COAs was found (Chi-square=8.32, df=1, p=0.004). G1- alleles of GABRB3 in COAs were significantly higher than in Non-COAs (Chi-square=6.622, df=1, p=0.022). We found no association of the polymorphic alleles of 5-HTTLPR with the COAs (Chi-square=0.021, df=1, p=0.884). There were significant associations between the type of parental alcoholism and depression of COAs. CONCLUSION: We found that the children of alcoholics had significantly increased genetic risk of alcohol drinking expectancy. This study provides some preliminary information on the risk and protective factors associated with the COAs, which can be used as a foundation for prevention and intervention of future psychopathology.
Alcohol Drinking ; Alcoholics* ; Alcoholism ; Alleles ; Child* ; Classification ; Depression ; Dopamine* ; Genotype ; Hospitals, Psychiatric ; Humans ; Korea* ; Parents ; Polymorphism, Genetic ; Psychopathology ; Receptors, Dopamine ; Receptors, Dopamine D4 ; Receptors, GABA-A* ; Risk Factors ; Serotonin Plasma Membrane Transport Proteins* ; Serotonin*