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Dopamine D4 Receptor Gene (dopamine + d4_receptor_gene)
Selected AbstractsAssociation Study Between Genetic Polymorphisms in the 14,3-3 , Chain and Dopamine D4 Receptor Genes and AlcoholismALCOHOLISM, Issue 3 2000H. Ishiguro Background: The dopaminergic system may be involved in the development of alcoholism. As part of our ongoing studies on the association between alcoholism and dopaminergic genes, we report herein a mutation analysis of the 14,3-3 , chain gene (YWHAH) and an association study between alcoholism and the YWHAH and dopamine D4 receptor gene (DRD4) polymorphisms. Methods: Nucleotide mutations were investigated using single-strand conformation polymorphism methods. Associations were analyzed using a case-control design involving 185 Japanese alcoholics and 286 Japanese controls. Results: Five polymorphisms, -147G>A, -134(GCCTGCA)2,4, IVS1+31(G)7,8. IVS1+73,74ins(G), and 753A>G, were detected on the YWHAH, and three of them were novel. No significant associations were found between alcoholism and these polymorphisms or two additional polymorphisms on DRD4 exon III and DRD4 -521C/T. Conclusions: YWHAH and DRD4 do not appear to play a major role in the development of alcoholism. [source] GENETIC STUDY: Polymorphisms of the dopamine D4 receptor gene (DRD4 VNTR) and cannabinoid CB1 receptor gene (CNR1) are not strongly related to cue-reactivity after alcohol exposureADDICTION BIOLOGY, Issue 2 2007Esther Van Den Wildenberg ABSTRACT Polymorphisms in the D4 dopamine receptor gene (DRD4) and the CB1 cannabinoid receptor gene (CNR1) have been associated with a differential response to alcohol after consumption. The goal of the present study was to investigate whether heavy drinkers with these polymorphisms would respond with enhanced cue-reactivity after alcohol exposure. Eighty-eight male heavy drinkers were genotyped for the DRD4 variable number of tandem repeats (VNTR) [either DRD4 long (L) or short (S)] and the CNR1 rs2023239 polymorphism (either CT/CC or TT). Participants were exposed to water and beer in 3-minute trials. Dependent variables of main interest were subjective craving for alcohol, subjective arousal and salivary reactivity. Overall, no strong evidence was found for stronger cue-reactivity (= outcome difference between beer and water trial) in the DRD4 L and CNR1 C allele groups. The DRD4 VNTR polymorphism tended to moderate salivary reactivity such that DRD4 L participants showed a larger beverage effect than the DRD4 S participants. Unexpectedly, the DRD4 L participants reported, on average, less craving for alcohol and more subjective arousal during cue exposure, compared with the DRD4 S participants. As weekly alcohol consumption increased, the CNR1 C allele group tended to report more craving for alcohol during the alcohol exposure than the T allele group. The DRD4 and CNR1 polymorphisms do not appear to strongly moderate cue-reactivity after alcohol cue exposure, in male heavy drinkers. [source] Association of DRD4 polymorphism with severity of oppositional defiant disorder, separation anxiety disorder and repetitive behaviors in children with autism spectrum disorderEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010Kenneth D. Gadow Abstract The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N = 66) were evaluated with a validated mother- and teacher-completed DSM-IV-referenced rating scale. Partial eta-squared (,p2) was used to gauge the magnitude of group differences: 0.01,0.06 = small, 0.06,0.14 = moderate and > 0.14 = large. Children who were 7-repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers' (,p2 = 0.10) and teachers' (,p2 = 0.06) ratings than noncarriers, but the latter was marginally significant (P = 0.07). Children who were 7-repeat allele carriers also obtained more severe maternal ratings of tics (,p2 = 0.07) and obsessions,compulsions (,p2 = 0.08). Findings for maternal ratings of separation anxiety were marginally significant (P = 0.08, ,p2 = 0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P = 0.05) for teachers' ratings of oppositional behavior and mothers' ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples. [source] Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2006Daniela Noaín Abstract The dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the extremely polymorphic nature of the human gene and the genetic association with attention deficit and hyperactivity disorder (ADHD). Several efforts have been undertaken to determine the D4R expression pattern in the brain using immunohistochemistry, binding autoradiography and in situ hybridization, but the overall published results present large discrepancies. Here, we have explored an alternative genetic approach by studying bacterial artificial chromosome (BAC) transgenic mice that express enhanced green fluorescent protein (EGFP) under the transcriptional control of the mouse dopamine D4 receptor gene (Drd4). Immunohistochemical analysis performed in brain sections of Drd4 -EGFP transgenic mice using an anti-EGFP polyclonal antibody showed that transgenic expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral agranular portions. In addition, discrete groups of Drd4 -EGFP labelled neurons were observed in the anterior olfactory nucleus, ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD. [source] Association Study Between Genetic Polymorphisms in the 14,3-3 , Chain and Dopamine D4 Receptor Genes and AlcoholismALCOHOLISM, Issue 3 2000H. Ishiguro Background: The dopaminergic system may be involved in the development of alcoholism. As part of our ongoing studies on the association between alcoholism and dopaminergic genes, we report herein a mutation analysis of the 14,3-3 , chain gene (YWHAH) and an association study between alcoholism and the YWHAH and dopamine D4 receptor gene (DRD4) polymorphisms. Methods: Nucleotide mutations were investigated using single-strand conformation polymorphism methods. Associations were analyzed using a case-control design involving 185 Japanese alcoholics and 286 Japanese controls. Results: Five polymorphisms, -147G>A, -134(GCCTGCA)2,4, IVS1+31(G)7,8. IVS1+73,74ins(G), and 753A>G, were detected on the YWHAH, and three of them were novel. No significant associations were found between alcoholism and these polymorphisms or two additional polymorphisms on DRD4 exon III and DRD4 -521C/T. Conclusions: YWHAH and DRD4 do not appear to play a major role in the development of alcoholism. [source] No association between a promoter dopamine D4 receptor gene variant and schizophreniaAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 6 2001Erik G. Jönsson Abstract The dopamine D4 receptor has been implicated in the pathogenesis of schizophrenia. An association between a putative functional promoter polymorphism (,521C/T) in the dopamine D4 receptor gene (DRD4) and schizophrenia was recently reported. In the present study, patients with schizophrenia (n,=,132) and control subjects (n,=,388) were analyzed with respect to the DRD4 ,,521C/T polymorphism. No significant case control differences emerged. The present results do not support a major role for DRD4 in the etiology of schizophrenia among Caucasians from Sweden. © 2001 Wiley-Liss, Inc. [source] Association of polymorphisms in the dopamine D4 receptor gene and the activity-impulsivity endophenotype in dogsANIMAL GENETICS, Issue 6 2007K. Hejjas Summary A variable number of tandem repeats (VNTR) polymorphism in exon 3 of the human dopamine D4 receptor gene (DRD4) has been associated with attention deficit hyperactivity disorder (ADHD). Rodents possess no analogous repeat sequence, whereas a similar tandem repeat polymorphism of the DRD4 gene was identified in dogs, horses and chimpanzees. Here, we present a genetic association study of the DRD4 VNTR and the activity-impulsivity dimension of the recently validated dog-ADHD Rating Scale. To avoid false positives arising from population stratification, a single breed of dogs (German shepherd) was studied. Two DRD4 alleles (referred to as 2 and 3a) were detected in this breed, and genotype frequencies were in Hardy,Weinberg equilibrium. For modelling distinct environmental conditions, ,pet' and ,police' German shepherds were characterized. Police German shepherds possessing at least one 3a allele showed significantly higher scores in the activity-impulsivity dimension of the dog-ADHD Rating Scale than dogs without this allele (P = 0.0180). This difference was not significant in pet German shepherds. To the best of our knowledge, this is the first report of an association between a candidate gene and a behaviour trait in dogs, and it reinforces the functional role of DRD4 exon 3 polymorphism. [source] | ||||||||||