The interaction between DRD4 gene rs1800955 polymorphism and negative life events on the personality characteristics of Mongolian adolescents / 中华行为医学与脑科学杂志

Objective To investigate the interaction between rs1800955 polymorphism of dopamine D4 receptor(DRD4) gene and negative life events on personality characteristics of Mongolian adolescents.Methods A total of 239 Mongolian adolescents aged 12-15 were assessed with Eysenck Personality Questionnaire(EPQ) and Adolescent Self-Rating Life Events Check List(ASLEC).The polymorphism of DRD4 gene rs1800955 was determined by improved multiple ligase detection reaction(iMLDR) technique.Results (1) The rs1800955 polymorphism of DRD4 gene was significantly correlated with psychoticism score of EPQ.The psychoticism score of individuals with CC genotype (4.94 ± 3.19) was higher than that of TT genotype (3.38±2.29),and the difference was statistically significant (P＜0.05).(2) The scores of psychoticism and neuroticism in Mongolian adolescents were positively correlated with the factors of negative life events(r=0.154-0.375,P＜0.05 or 0.01).(3) The interaction between the rs1800955 polymorphism of DRD4 gene and negative life events significantly affected the scores of psychoticism in Mongolian adolescents (C C genotype x interpersonal factor:B =-2.689,95 ％ CI =-4.589--0.789,x2 =7.695,P＜ 0.01).In individuals with CC genotype,the scores of psychoticism in those with high scores of interpersonal relatioriship factors were significantly higher than those with low scores of interpersonal relationship factors ((3.01 ± 0.71) vs (2.61 ±0.67);t =-3.066,P＜ 0.01).Conclusion The polymorphism of DRD4 gene rs 1800955 and its association with interpersonal factors play an important role in the psychoticism of Mongolian adolescents.The CC genotype is a risk factor of psychoticism,and the poor interpersonal relationship may increase the risk of individuals with CC genotype.

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 dopamine D4 receptor gene variants with autism.

Background: Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with poorly understood and complex etiology. The central dopaminergic system is strongly implicated in ASD pathogenesis. Genes encoding various elements of this system have been linked to ASD. This study aimed to estimate the distribution frequency of dopamine D4 receptor-exon III repeat region polymorphic genotypes among Egyptian children with autism. Methods: This case-control study included 178 children with autism (mean age 4.46±1.72 years) (118 males and 60 females) and a normal control group (n=128) of matching age and gender. Assessments by DSMIV- TR criteria, Stanford-Binet intelligence scale and childhood autism rating scale (CARS) were done. Assay for DRD4 48 bp VNTR genotypes was performed on amplified DNA by RFLP-PCR. Results: The 4/4 allele had the highest frequency among both autistic (39.32%) and control children (62.5%), with no significant difference between them. The 7/7 allele had also a high frequency (33.7%) among autistic patients, which was significantly different (p˂0.05) from the control group (12.5%) Furthermore, 70% of the patients carrying the 7/7 allele had the lowest IQ scores (58.5±6.5). Conclusions: There is a strong evidence that the DRD4 7/7 allele might be a risk factor for autism.

Identification and Characterization of Dopamine D4 Receptor (DRD4) Gene Sequence within and Among Non Mammalian Species.

A number of polymorphic tandem repeats in human dopamine D4 receptor (DRD4) have been identified in the exons, including a 12-bp repeat in the first exon and a 48-bp repeat in exon III located in the third cytoplasmic loop. However, to determine whether the tandem repeats is specific to humans or not, we have identified and characterized dopamine receptor D4 (DRD4) Exon III tandem repeats in public available nucleotide sequences from 13 different non mammalian species. We found that the tandem repeat was composed of 21-bp modules in sequences from the Mycobacterium smegmatis str. MC2 155, Salinibacter ruber DSM 13855, Danio rerio, Parus major, Corvus macrorhynchos, and Coturnix japonica. A tandem repeat consisting of 30-bp modules was identified in sequence from Melopsittacus undulates while in the Phalacrocorax capillatus and Numida meleagris we identified tandem repeats composed of 3-bp modules. Tandem repeats could not be identified in sequences from Carassius auratus, Phasianus colchicus and Gallus gallus. To understand the evolutionary history of the Exon I region of DRD4—which in humans contains a polymorphic 12bp tandem duplication, a polymorphic 13bp deletion, and other rare variants—we examined the homologous exon in these different species. There was a low degree of similarity between the sequences of bacterial species and those from members of the piscean and avian and with human sequence. We identified transmembrane domain of DRD4 gene and signature of G-protein coupled receptors in the amino acid sequences. The number of transmembrane segments varied pronouncedly between species from 0 to 7 and signature of G-protein coupled receptors was found only in piscean species and was also identified in one avian species (parus major). These findings suggest that an association between Drd4 gene polymorphisms and animal personality variation predates the divergence of the non mammalian and mammalian lineages. Furthermore, the analysis of Drd4 polymorphisms within and among populations may provide information for elucidating the phylogenetic relationship and such data may also provide a clue toward understanding the relation between the genetic variation and behavioral variation in animals.

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.

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.