Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An excess dopaminergic activity may be implicated in the etiology of schizophrenia. Our objective was to identify nucleotide variants in the 5' region of the dopamine D2 receptor gene (DRD2) and to clarify their effects on schizophrenia. We identified two polymorphisms, the A-241G and -141C Ins/Del, by examination of 259 bp in the 5'-flanking region and 249 bp of exon 1 of DRD2. Reporter constructs containing the -141C Del allele cloned into a luciferase reporter plasmid drove 21% (Y-79 cells) and 43% (293 cells) expression compared with the -141C Ins allele. In a case-control study, the -141C Del allele frequency was significantly lower in 260 schizophrenic patients than in 312 controls (OR = 0.60, 95%CI 0.44-0.81, P < 0.001). No significant association was found between the A-241G polymorphism and in vitro luciferase activity, or in allele frequency between the patients versus controls. These findings show that the -141C Ins/Del may be a functional polymorphism in the 5'-promoter region of DRD2 and may affect the susceptibility to schizophrenia.
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PMID:A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. 909 61

A possible dysregulation of dopaminergic neurotransmission has been implicated in the aetiology of schizophrenic psychoses, in particular of paranoid-hallucinatory states, and of the manic episodes of bipolar affective disorder. In the present study we analysed allelic and genotypic variations of a recently described functional deletion/insertion variant (-141C Ins/Del) in the 5' flanking region of the human dopamine D2 receptor gene. We investigated a total of 620 unrelated individuals, comprising 260 schizophrenic patients, 70 patients with bipolar affective disorder, and 290 population controls. Analysis of the -141C Ins/Del variant revealed that the schizophrenic, bipolar affective and control groups did not differ significantly regarding genotype frequencies and allele frequencies. No evidence of an allelic association with either a family history of schizophrenic psychosis or a diagnosis of schizophrenia of the paranoid type (according to ICD 10) was found. Our findings indicate that the -141C Del variant in the 5' flanking region of the human dopamine D2 receptor gene is unlikely to play a substantial role in genetic predisposition to major psychiatric disorders in Caucasians.
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PMID:Insertion/deletion variant (-141C Ins/Del) in the 5' regulatory region of the dopamine D2 receptor gene: lack of association with schizophrenia and bipolar affective disorder. Short communication. 958 64

Several studies showed the density of D2 receptors was elevated in postmortem brains from schizophrenics. Genes which operate at the level of gene activation may be associated with the pathogenesis of schizophrenia. Arinami et al. [(1997) Human Molecular Genetics 6, 577-582] found a polymorphism in the 5'-flanking region of the D2 receptor gene designated as -141C Ins/Del. The promoter activity by luciferase assay of a plasmid containing the -141C Ins allele was higher than in the one containing the -141C Del allele. In addition, the -141C Ins allele frequency was significantly higher in schizophrenics than in control subjects. We replicated the -141C Ins/Del polymorphism in 170 schizophrenics and 121 healthy control subjects. The number of schizophrenics with the -141C Ins/Ins genotype was significantly higher than that of control subjects (P = 0.038). The frequency of the -141C Ins allele was significantly increased in the schizophrenics compared with the control subjects (P = 0.042). The mean age of onset for the patients with -141C Ins/Del was significantly lower than that for the patients with -141C Ins/Ins (P = 0.029). There was no association between the genotype and either positive symptoms or the response to antipsychotic medication. Our results suggest that the -141C Ins/Del polymorphism may affect the susceptibility to schizophrenia.
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PMID:Functional polymorphism of -141C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia. 985 29

Dopamine receptors are strong candidates for involvement in schizophrenia and are targeted by a wide variety of antipsychotics. We hypothesized that genetic variation in these neurotransmitter receptors may influence clinical response to clozapine, an antipsychotic which displays high affinity for dopamine D2 receptors in the limbic system. To test this hypothesis, we studied a functional polymorphism in the promoter region of the D2 receptor gene (-141C Ins/Del) in a sample of 151 clozapine treated patients of British origin. In addition, the influence of this polymorphism on antipsychotic response in general was investigated on a sample of 146 Han Chinese schizophrenic patients treated with a variety of antipsychotics. No association was found between this polymorphism and clinical response in either of the two samples suggesting that genetic variation in D2 receptors does not play a major role in determining clinical response to antipsychotic treatment.
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PMID:Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response. 991 31

A functional polymorphism in the promoter region of the dopamine D2 receptor gene, the -141C Del allele, which may be associated with schizophrenia susceptibility, has previously been described in a Japanese sample. The present study was done in order to examine whether such an association would also be found in a North American schizophrenia patient population. However, analysis of the -141C Del allele frequency in the present group of schizophrenia patients (n = 50) and control subjects (n = 51) did not identify any significant differences. These data support the recent reports on German and British subjects that this genetic variation in the 5'-flanking region of the dopamine D2 receptor gene does not play a major role in the genetic predisposition to schizophrenia.
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PMID:Dopamine D2 receptor promoter polymorphism: no association with schizophrenia. 1022 12

Genetic factors and dopamine receptor dysfunction have been implicated in the pathophysiology of schizophrenia. Recently, an association between a putative functional promoter polymorphism (-141C Ins/Del) in the dopamine D2 receptor gene and schizophrenia was reported. We investigated unrelated Swedish schizophrenic patients (n = 129) and control subjects (n = 179) for the same polymorphism. Similarly to a previous Japanese report, the - 141C Del allele frequency was significantly lower in patients than controls (chi2=4.4, 1 df, p<0.05; odds ratio 0.49, 95% confidence interval 0.26-0.91). The present and previous results may indicate that the -141C Ins/Del dopamine D2 receptor gene polymorphism affects susceptibility to schizophrenia.
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PMID:Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia. 1054 Oct 4

The Del allele of the -141C (Ins/Del) polymorphism located in the immediate 5'-flanking region of the human dopamine D2 receptor gene has been reported to be associated with reduced promoter activity in vitro. However, genetic association studies of the -141C (Ins/Del) polymorphism with schizophrenia and alcoholism have yielded conflicting results. In this report, we explored the effect of the Del allele on the D2 receptor binding characteristics in vivo in healthy volunteers using positron emission tomography and D2 receptor antagonist, [11C]raclopride. No difference in D2 receptor density was observed between the Del allele carriers compared to the individuals with the Ins/Ins genotype, indicating that the genetic variation at the -141C (Ins/Del) site does not affect D2 receptor expression level in vivo.
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PMID:The dopamine D2 receptor 5'-flanking variant, -141C Ins/Del, is not associated with reduced dopamine D2 receptor density in vivo. 1078 Feb 70

To replicate a previously found negative association between the Del allele of the -141C Ins/Del polymorphism in the 5'-promoter region of the dopamine D2 receptor gene (DRD2) and schizophrenia in Japanese subjects and to examine whether this polymorphism is related to the features of antipsychotic drug treatment, we genotyped 94 control subjects and 234 schizophrenic patients. The schizophrenic patients had a significantly lower frequency of the Del allele (p < 0.05). We found a non-significant trend towards a higher frequency of the Del allele in schizophrenic patients susceptible to neuroleptic-induced extrapyramidal symptoms. The daily dosage of haloperidol, the steady-state concentration of serum haloperidol per daily dosage, and the recent 1-yr cumulative neuroleptic dosage were lower in patients with the Del/Del genotype than in the other patients. These findings support the view that the polymorphism is associated with schizophrenia in Japanese subjects and provide hints for further attempts to establish the relationship between this polymorphism and the features of antipsychotic drug treatment.
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PMID:Association between a polymorphism in the promoter region of the dopamine D2 receptor gene and schizophrenia in Japanese subjects: replication and evaluation for antipsychotic-related features. 1128 87

The dopamine D2 receptor (DRD2) gene has been listed as one of the candidate genes for susceptibility to schizophrenia. To date, a significant association between schizophrenia and two functional DRD2 gene polymorphisms, Ser311Cys and -141C Ins/Del, in Japanese samples, has been reported by Arinami et al. [1994: Lancet 343:703-704; 1997: Hum Mol Genet 6:577-582]. In the present study, we replicated the findings of Arinami et al. [1994: Lancet 343:703-704; 1997: Hum Mol Genet 6:577-582] in the same ethnic groups (Japanese samples) with the same polymorphisms (Ser311Cys and -141C Ins/Del). We genotyped these two polymorphisms for 241 patients and for 201 controls. Neither polymorphism was associated with schizophrenia. Moreover, in a haplotype analysis of the present sample, combined pairs of two polymorphisms provided no evidence for the association of either haplotype with schizophrenia. Our findings indicate that an association between the two functional DRD2 gene polymorphisms, Ser311Cys and -141C Ins/Del, and schizophrenia is unlikely.
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PMID:Association analysis between two functional dopamine D2 receptor gene polymorphisms and schizophrenia. 1130 33

Previous studies have demonstrated a lower density of dopamine D2 receptor (DRD2) in subjects without Del alleles of the -141C Ins/Del polymorphism in DRD2 gene promoter region than in those with one or two Del alleles. The present study aimed to examine whether the -141C Ins/Del DRD2 promoter polymorphism is related to therapeutic response to selective DRD2 antagonists in the treatment of schizophrenia. Subjects consisted of 49 acutely exacerbated schizophrenic inpatients treated with bromperidol (30 cases, mean dose +/- SD: 11.4 +/- 4.8 mg/day) or nemonapride (19 cases, 18 mg/day). Clinical symptoms were evaluated by the Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment. The -141C Ins/Del DRD2 genotypes, the Ins and Del alleles, were determined by a polymerase chain reaction method. Thirty-five patients were homozygous for the Ins allele and 14 were heterozygous for the Del and Ins alleles. The patients without Del allele showed a higher percentage of improvement in anxiety-depression symptoms than those with Del allele (58.5 +/- 44.5% versus 24.1 +/- 48.2%) after 3 weeks of treatment while percentage improvement in total BPRS or other subgrouped symptoms (positive, negative, excitement and cognitive symptoms) was similar between the two genotype groups. The present results suggest that the -141C Ins/Del DRD2 polymorphism is associated with anxiolytic and antidepressive effects of neuroleptic treatment in schizophrenic patients.
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PMID:The -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter region is associated with anxiolytic and antidepressive effects during treatment with dopamine antagonists in schizophrenic patients. 1150 24


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