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)

Disturbances in dopamine neurotransmission have been postulated to underlie schizophrenia. We report data from two independent studies of a BalI polymorphism in the dopamine D3 receptor gene in patients with schizophrenia. In both studies, more patients than controls were homozygous (p = 0.005, p = 0.008). When pooled data were analysed, this difference was highly significant (p = 0.0001) with a relative risk of schizophrenia in homozygotes of 2.61 (95% confidence intervals 1.60-4.26).
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PMID:Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. 841 Oct 64

The dopamine hypothesis of schizophrenia proposed that dopaminergic pathways are involved in the etiology of the disease. In particular, interest among psychiatrists has focused on the D2 receptor because of its affinity to antipsychotic drugs. Recently a new dopamine receptor gene has been cloned, and named the dopamine D3 receptor. The D3 receptor is a potential site for antipsychotic drug action and may be involved in the pathophysiology of schizophrenia. We have carried out a linkage study between the susceptibility gene for schizophrenia and polymorphism of the dopamine D3 receptor gene in two Japanese pedigrees. The LOD scores were negative for all genetic models and for all affective status at a recombination fraction theta = 0. Linkage of DRD3 has been excluded for the model 1 (dominant model) and the model 3 (recessive model). The LOD score was -3.43 at theta = 0 for model 1 (dominant model) and broad definition of affected status. These results were consistent with previous studies.
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PMID:Further evidence of no linkage between schizophrenia and the dopamine D3 receptor gene locus. 781 May 86

We have reported an association between schizophrenia and homozygosity of a Bal I polymorphism in the first exon of the dopamine D3 receptor gene (Crocq et al.: Journal of Medical Genetics 29:858-860, 1992). The present study consists of an attempt to replicate this finding in a further sample of 66 patients and 97 controls. Once again more patients than controls were homozygous, but the effect was not as strong as in our first study (chi 2 = 2.53, P = 0.05, one tailed). When pooled data from our two studies were analysed, excess homozygosity in patients remained highly significant (P = 0.002) with a particular excess of the 1:1 genotype (P = 0.01). This reflected a departure from Hardy-Weinberg equilibrium in the patients (P = 0.0005) but not the controls (P = 0.24). This led us to explore the possibility that there might be important differences between the patients in our two studies and that excess homozygosity might be a characteristic of particular subgroups of schizophrenics. Our findings suggest that the effect is consistently at its strongest in those patients who have a high familial loading and in those who have a good response to neuroleptic treatment, and that differences between our two samples might have contributed to the quantitatively different outcomes.
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PMID:Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia. 790 89

The finding of contrasting results regarding an association between schizophrenia and the MscI polymorphism site in the dopamine D3 receptor gene prompted us to study the distribution of this polymorphism in an Italian sample of 52 patients suffering from delusional disorder, 85 schizophrenic patients and 78 control subjects. No significant differences in genotype, allele and homozygosity frequencies between schizophrenics and controls were found, while a significant, albeit modest, association was discovered between delusional disorder and both the 1 allele and the 1-1 genotype. This suggests a contribution of this gene to the liability to develop delusional disorder.
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PMID:Distribution of the MscI polymorphism of the dopamine D3 receptor in an Italian psychotic population. 791 42

Bipolar affective disorder and schizophrenia share many clinical and genetic characteristics, and are thought by some to be different expressions of the same underlying disorder. A recent study showed an excess of homozygosity at a BalI polymorphism in the dopamine D3 receptor gene in schizophrenic patients compared with controls, from two independent centres. We have found no evidence of such an excess in a comparable sample of patients with bipolar affective disorder compared with matched controls. If these findings are confirmed then at least one genetic distinction between these two disorders will have been ascertained and doubt cast upon theories of a common genetic aetiology.
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PMID:The dopamine D3 receptor gene: no association with bipolar affective disorder. 809 68

The recently discovered dopamine D3 receptor can be considered as a D2-like receptor: it is encoded by a gene comprising several introns; it is both an autoreceptor and a postsynaptic receptor, well recognized by antipsychotics. It differs, however, from the D2 receptor by a much more discrete expression, mostly in few limbic brain areas, e.g. shell of nucleus accumbens, islands of Calleja, and a considerably higher affinity for dopamine. Two association studies preliminarily suggest that the homozygotes for a D3 receptor gene polymorphism display twofold higher risk of schizophrenia, whereas several linkage studies led to inconclusive results.
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PMID:Dopamine D3 receptor: basic and clinical aspects. 810 95

Using a case-control design, a reported association of schizophrenia with homozygosity at the dopamine D3 receptor gene locus was investigated in a group of patients (n = 53), with schizophrenia (DSM-III-R), and psychiatrically normal controls (n = 61), matched for ethnicity and area of residence. No significant differences in the distribution of alleles or genotypes between the two groups could be detected. However, among patients with a family history of schizophrenia, as compared to controls without such family history, an association with allele 1 at this locus was noted (Odds ratio 12.4, C.I. 1.61, 96.35).
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PMID:Association study of schizophrenia with dopamine D3 receptor gene polymorphisms: probable effects of family history of schizophrenia? 813 4

Dopamine receptor dysfunction has been implicated in the pathophysiology of schizophrenia. Schizophrenic patients (n = 76) and control subjects (n = 53) were examined for allele frequencies in a 2-allele BalI polymorphism, causing a serine-->glycine amino acid substitution in the coding sequence of the dopamine D3 receptor gene. No statistical significant differences of allele frequencies or genotype frequencies could be found between the two groups. Neither were there any significant relationships between allele frequencies and a number of clinical variables within the schizophrenic subsample. However, if not corrected for multiple testing, an association was found between homozygosity and positive response to neuroleptic drugs. The present study does not provide evidence that the BalI polymorphism in the dopamine D3 receptor gene is involved in the pathophysiology of schizophrenia. Further investigations with an increased number and variety of patients concerning response to neuroleptic drugs and expression of the receptor in human brain should be performed to definitively exclude this hypothesis.
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PMID:Lack of association between schizophrenia and alleles in the dopamine D3 receptor gene. 851 75

We examined a Ser-9-Gly polymorphism in the dopamine D3 receptor gene for allelic association with schizophrenia in 133 patients currently treated with clozapine and 109 controls. Allele 1 (Ser-9) was significantly more frequent in the patients (69%) than in the controls (56%) (P = 0.004). The 1-1 genotype was more common (43% vs 30%) and the 2-2 genotype less common (5% vs 18%) in patients than in controls. When the patient group was subdivided on the basis of clinical response to clozapine, using a 20-point improvement in the global assessment scale as cut-off, genotype 1-1 was found to be more frequent among the non-responders (53% vs 36%, P = 0.04). To place our results in the context of previous studies of this polymorphism and schizophrenia, we performed a meta-analysis of all published data including the present sample. The combined analysis shows evidence for a modest association between genotype 1-1 and schizophrenia (odds ratio 1.25, 95% confidence interval 1.05-1.49, P = 0.01). These results suggest that the Ser-9 allele, or a nearby polymorphism in linkage disequilibrium, results in a small increase in susceptibility to schizophrenia.
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PMID:Allelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia. 864 85

DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D3 receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The Msp I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the Bal I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distribution of the Msp I and Bal I genotypes were not independent in 297 individuals (chi 2 = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the Bal I polymorphism and allele 2 of the Msp I polymorphism (chi 2 = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the Bal I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-III-R chronic schizophrenics and 85 controls (chi 2 = 5.3, df = 1, P = 0.02) and found more important in mal than in females. The presence of the Bal I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts, and proportion of homozygotes for the Msp I polymorphism did not differ between schizophrenics and controls (chi 2 = 0.06, df = 1, P = 0.80, chi 2 = 0.22, df = 1, P = 0.90 and chi 2 = 0.16, df = 1, P = 0.69, respectively). The large distance of the Msp I polymorphism from the Bal I polymorphism and its localization in the 3' part of the gene may explain the discrepant results obtained with the two polymorphisms.
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PMID:Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia. 867 17


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