DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo

Objective: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3′-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). Methods: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. Results: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. Conclusion: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.

Dopamine D4 Receptor Gene Associated with the Frontal-Striatal-Cerebellar Loop in Children with ADHD: A Resting-State fMRI Study / 神经科学通报·英文版

Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.

Association of gender, age, education and polymorphism of DRD4 gene with cognitive functions in adults / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of cognitive functions with gender, age, education and polymorphism of dopamine receptor D4 (DRD4) gene in healthy adults.</p><p><b>METHODS</b>Four hundred and fifty-five healthy participants have completed 3 cognitive function tests including Tower of Hanoi (TOH), Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT). Peripheral blood samples were collected from all participants, and genomic DNA was extracted according to a standard phenol-chloroform procedure. Rs3758653 in the promoter region of the DRD4 gene was genotyped using Illumina GoldenGate genotyping assay.</p><p><b>RESULTS</b>Males have performed better than females in terms of TOH executive time and TOH total score, but did worse in TOH planning time. Most of the measured cognitive domains were affected by age and education. Cognitive ability has decreased along with increased age and decline of educational years. The polymorphism of rs3758653 has mainly correlated with the TOH executive time. Compared with A allele carriers, G allele carriers did worse in TOH executive time.</p><p><b>CONCLUSION</b>Gender, age, education and the rs3758653 polymorphism of the DRD4 gene play an important role in cognitive functions in healthy adults.</p>

Association of 5-HTTLPR, DRD4 gene polymorphisms with the accident tendentiousness of drivers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between 5-HTTLPR and/or DRD4 gene polymorphisms and the accident tendentiousness of drivers.</p><p><b>METHODS</b>A case-control study, including 42 patients and 46 controls, were performed using type-A behavior questionnaire and EPQ scale. 5-HTTLPR and DRD4 gene -521 C/T were detected by the PCR-RFLP technique.</p><p><b>RESULTS</b>The scores of type-A behavior questionnaires, such as TH and TH + CH in exposure group were significantly higher than those in control group (P < 0.05). P and N scores of EPQ questionnaires in exposure group were significantly higher than those in control group, and L score in exposure group was significantly lower than that in control group (P < 0.05 or P < 0.01). There were significant differences in the frequencies of the genotypes and alleles of 5-HTTLPR gene between the cases and the controls (P < 0.05), but there were no significant differences in the frequencies of the genotypes and alleles of DRD4 gene between the two groups (P > 0.05). In the drivers with the accident tendentiousness, P scores in the cases with homozygous genotypes of the S/S in 5-HTTLPR gene were significantly higher than those in the cases with the genotypes of S/L and L/L in 5-HTTLPR gene (P > 0.05). E scores in subjects with homozygous genotypes of the T/T in DRD4 gene were significantly higher than those in subjects with genotypes of the T/C+C/C in DRD4 gene (P > 0.05).</p><p><b>CONCLUSION</b>The driver accident tendentiousness may be associated with 5-HTTLPR gene, but not associated with DRD4 gene. The two genes are associated with the type-A behavior and personality characteristics of drivers with accident tendentiousness. However, 5-HTTLPR and DRD4 gene may not have synergism in these behaviors and personality.</p>

The Association among the Genetic Polymorphism of Dopamine D4 Receptor, Temperament and Alcohol Drinking Behavior in Young Korean Adults

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.

The Association between DNA Polymorphisms and Smoking Cessation in Korean Smokers

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.

Association of 14 polymorphisms in the five candidate genes and attention deficit hyperactivity disorder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Attention 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.</p><p><b>METHODS</b>One 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.</p><p><b>RESULTS</b>1.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%.</p><p><b>CONCLUSIONS</b>The 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.</p>

Association between Dopamine D4 Receptor Gene Polymorphism and Scores on a Continuous Performance Test in Korean Children with Attention Deficit Hyperactivity Disorder

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.

Genetic Polymorphisms in Dopamine- and Serotonin-Related Genes and Treatment Responses to Risperidone and Perospirone

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.

Relationship between dopamine D4 receptor gene polymorphisms and primary nocturnal enuresis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study polymorphisms of dopamine D4 receptor (DRD4) in children with primary nocturnal enuresis (PNE) and explore the relationship between DRD4 gene polymorphisms and PNE.</p><p><b>METHODS</b>Genomic 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.</p><p><b>RESULTS</b>There 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).</p><p><b>CONCLUSIONS</b>The 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.</p>

Association Study of Dopamine D2, D4 Receptor Gene, GABA(A) Receptor beta Subunit Gene, and Serotonin Transporter Gene Polymorphism with Children of Alcoholics in Korea: Preliminary Study / 신경정신의학

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.

Association between the polymorphism in the promoter region of dopamine D4 receptor gene and chronic tic disorder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study a possible association between the three functional polymorphisms in the promoter region of dopamine D4 receptor (DRD4) gene and chronic tic disorder.</p><p><b>METHODS</b>Genomic DNA was isolated from the venous blood leukocytes of 84 unrelated patients with chronic tic disorder (Study group) and 100 healthy unrelated individuals (Control group). Polymorphisms of DRD4, 1240L/S, 616C/G and 521C/T, were genotyped by the allele-specific primer (ASP) PCR. Genotype, allele and haplotype frequencies were analysed by SHEsis online.</p><p><b>RESULTS</b>There were significant differences in both allele and genotype frequencies (chi(2) = 8.419, P < 0.01; chi(2) = 7.860, P < 0.05 respectively) of DRD4-616C/G between the Study and the Control groups. Haplotypic frequencies of LCT (1240L/S, 616C/G, 521C/T) in the Study group were noticeably higher than in the Control group (chi(2) = 6.371, P < 0.05).</p><p><b>CONCLUSIONS</b>There is an association between the DRD4-616C/G polymorphism and chronic tic disorder. The individuals with haplotype LCT (1240L/S, 616C/G, 521C/T) are susceptible to this disorder.</p>

Lack of Association between Polymorphisms of the Dopamine Receptor D4 and Dopamine Transporter Genes and Personality Traits in a Korean Population

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.

Distribution of genotype and allele frequencies of dopamine D4 receptor gene 48 bp variable number tandem repeat polymorphism in Chinese Han population in Hunan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the distribution of genotype and allele frequencies of the dopamine D4 receptor(DRD4) gene exon 3 48 bp variable number of tandem repeats polymorphism in Hunan Han population.</p><p><b>METHODS</b>The genotype and alleles of 304 healthy persons were examined with polymerase chain reaction, denaturing polyacrylamide gel electrophoresis and silver staining.</p><p><b>RESULTS</b>Seven alleles and twelve genotypes were found. The most common allele was allele 5 with a frequency of 70.6%. There was statistically significant difference in allele distribution between the Hunan Han population and the Han population of other regions such as Shanghai, Beijing and Sichuan in China (P< 0.05). Different allele frequency distributions were observed when compared to other ethnic populations such as Japanese, American, Mexican, and Italian (P< 0.05).</p><p><b>CONCLUSION</b>The distributions of allele of DRD4 gene exhibit regional and ethnic heterogeneity.</p>

Association of Dopamine D4 Receptor Gene(DRD4) VNTR Polymorphism and Response to Methylphenidate Treatment in Korean ADHD Children / 신경정신의학

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.

Molecular pharmacogenetic studies of drug responses to obsessive-compulsive disorder and six functional genes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the associations between the drug responses to obsessive -pulsive disorder (OCD) and six functional genes related with serotonin and dopamine.</p><p><b>METHODS</b>One hundred and thirteen OCD nuclear families were collected. The OCD patients were treated with serotonin reuptake inhibitors (SRIs) for 8 weeks and the drug responses were assessed using the Yale-Brown obsessive-compulsive scale (Y-BOCS). The patients were divided into drug responders group and non-responders group according to the reducing rate of Y-BOCS score. The genotypes of six genes were determined with the Amp-FLP and Amp-RFLP techniques and analyzed by transmission disequilibrium test (TDT). The six genes are serotonin 2A receptor (5-HT2A), serotonin transporter (5-HTT), dopamine D2 receptor ( DRD2), dopamine D4 receptor (DRD4), catechol-O- methyltransferase (COMT) and monoamine oxidase A (MAOA).</p><p><b>RESULTS</b>No association was found between the six genes and different drug responses groups. However, there was significant difference between the drug responders and non-responders in homozygosity at the 5-HT2A -1438G/A locus (chi(2)=4.69, P=0.03).</p><p><b>CONCLUSION</b>The results suggested that the 5-HT2A may play some roles in the effects of drug treatment on OCD.</p>

Associations between six functional genes and schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the associations between schizophrenia and six functional genes: dopamine D2 receptor gene (DRD2), dopamine D4 receptor gene (DRD4), 5-hydroxytryptamine 2A receptor gene (5-HT2A), 5-HT6 receptor gene (5-HT6), catechol-O-methyltransferase gene (COMT) and dopamine transporter gene (DAT1).</p><p><b>METHODS</b>With the techniques of Amp-RFLP and Amp-FLP, association analysis was made between schizophrenia and the six genes in 67 schizophrenic patients from Chinese Han population.</p><p><b>RESULTS</b>(1) Neither genotypes nor alleles of DRD2, 5-HT2A, 5-HT6 and COMT gene showed significant differences between patients and controls (P>0.05). (2) Six repeats (6R) in DRD4 gene, the allele of 480 bp and the genotype of 480/520 in DAT1 gene were found to be of significant differences between the two groups (P<0.05). (3) Only one negative association was observed between the 480 bp allele of DAT1 gene and schizophrenia (OR=0.441, 95% CI:0.202-0.963, Z=2.05, P<0.05).</p><p><b>CONCLUSION</b>The 480 bp allele of DAT1 gene is negatively associated with schizophrenia in Chinese Han population, which stands for the dopamine hypothesis of schizophrenia.</p>

Transmission disequilibrium test of DRD4 exon III 48bp variant number tandem repeat polymorphism and tic disorder / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate whether DRD4 exon III48 bp variant number tandem repeat(VNTR) polymorphism is associated with tic disorder.</p><p><b>METHODS</b>One hundred and twenty-two nucleus families were collected using Structured clinical interview for genetic study of Tourette syndrome and related disorders for family-based association analysis of tic disorder and DRD4 exon III 48bp VNTR polymorphism. One hundred and twenty-two trios were divided into two groups: tic disorder group (82 trios of Tourette syndrome or chronic tic disorder, TS&CT) and tic disorder accompanied with attention deficit and hyperactivity disorder (ADHD) group (40 trios of Tourette syndrome or chronic tic disorder accompanied with ADHD, TS&ADHD). Transmission disequilibrium test (TDT), in addition to polymerase chain reaction and VNTR technique were conducted in 122 trios.</p><p><b>RESULTS</b>There exist 5 alleles at this polymorphic locus in this sample including DRD4 exon III 48bp 2-6 repeats. No transmission disequilibrium was found between DRD4 exon III 48 bp VNTR and tic disorder (chi square=7.44, P 0.12); however, when the sample was divided into two groups, transmission disequilibrium was noticed between the cases of TS&ADHD and this locus by overall allele-wise analysis (chi square=11.74, P 0.02), and there exists transmission disequilibrium exclusively between 5 or 6 repeats of 48bp VNTR(longer alleles) by allele-wise analysis (chi square=10.57, P 0.032, chi square=6.13, P 0.01). No transmission disequilibrium was seen between TS&CT and DRD4 exon III 48bp VNTR(chi square=3.38, P 0.50).</p><p><b>CONCLUSION</b>The results of this study have revealed an association between the longer alleles of DRD4 exon III 48bp VNTR polymorphism and tic disorder accompanied with ADHD, thus suggesting a possible genetic risk factor of tic disorder accompanied with ADHD in Chinese.</p>

Allelic Association of the Dopamine D4 Receptor Gene in Korean Alcoholism

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.

Association of Dopamine D4 Receptor(DRD4) Gene Polymorphism with Korean Schizophrenic Patients

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.