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)

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

Our work investigates the relationship between genetic factors and schizophrenia, seeking to identify a gene or genes associated with the clinical form of the disease in a group of Italian patients. In pursuit of the 'dopaminergic hypothesis' of schizophrenia, we explored a possible etiologic role of two dopamine receptor genes, DRD3 and DRD4, that have been repeatedly suggested as factors in the pathophysiology of the disease. We typed DNA polymorphisms in each of the genes that code for variation in the amino acid sequence of the receptor protein. An innovative design using parental chromosomes as controls--the 'haplotype relative risk' strategy--represents a significant improvement over previous association studies in psychiatric genetics. Our results suggest that, at least in our well-defined population, the candidate genes DRD3 and DRD4 do not appear to play a major role in the genetic etiology of schizophrenia.
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PMID:An association study between schizophrenia and the dopamine receptor genes DRD3 and DRD4 using haplotype relative risk. 786 86

A study of the genetic association between schizophrenia and a BalI polymorphism in exon 1 of the dopamine D3 (DRD3) gene, a candidate gene for schizophrenia, was conducted. The polymorphism was examined in 91 patients whose symptoms satisfied DSM-III-R for schizophrenia and 90 controls. There were no significant differences between the groups in allele frequencies or genotype counts. Contrary to a previous report, the patients were no more likely to be homozygous than controls. Moreover, no association with the presence of illness could be demonstrated when the patients were grouped according to sex, age of onset, history of admission to psychiatric institutions or positive family history.
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PMID:A study of the association between schizophrenia and the dopamine D3 receptor gene. 822 13

The D3 dopamine receptor gene is an important candidate gene for schizophrenia, since--because of its almost exclusive expression in the limbic system--it combines the dopamine receptor hypothesis with the limbic system hypothesis of schizophrenia. Pairwise linkage analyses were carried out between the D3 dopamine receptor gene locus (DRD3) and schizophrenia (including major depression among its pleiotropic manifestations). On the basis of these analyses, which assumed a penetrance of 0.71 and a dominant mode of inheritance, we were able to exclude the DRD3 locus with a lod score of -2.50 in four Icelandic pedigrees. The area of exclusion (lod score < -2.00) extended 1.2 centimorgans. We conclude that the genetic predisposition to schizophrenia in these pedigrees is not due to a mutation in the DRD3 locus. However, these results cannot exclude the possibility that a defect in other genes regulating the expression of the D3 dopamine receptor gene could be involved in the pathogenesis of schizophrenia or that linkage analyses in other families or population-based association studies might show a positive result.
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PMID:No evidence of linkage between schizophrenia and D3 dopamine receptor gene locus in Icelandic pedigrees. 846 57

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

A missense polymorphism (glycine to serine) in the first exon of the dopamine D3 (DRD3) gene was examined in the sib-pairs schizophrenia collection by the transmission test for linkage disequilibrium (TDT). No association due to linkage disequilibrium was detected using TDT. Additionally, no evidence for excess homozygosity was found.
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PMID:No association detected between a D3 receptor gene-expressed variant and schizophrenia. 872 55

Disturbances in the dopaminergic transmission have been implicated in the etiology of schizophrenia. Recently, an association of schizophrenia with increased homozygosity of a Gly9/Ser9 polymorphism in the dopamine D3 receptor gene (DRD3) has been reported (Crocq et al., 1992; Mant et al., 1994). This finding reflected a departure from the Hardy-Weinberg equilibrium in the genotype distribution observed in schizophrenic patients. The effect was found to be at its strongest in patients with a high familial loading. In the present study, we tried to replicate this finding in a sample of 146 German patients with a DSM-III-R diagnosis of schizophrenia. All patients had a positive family history of major psychiatric disorder including 70 patients with a family history of schizophrenia. Given our sample size, we have a power of 99.8% to detect 2. deviation from the Hardy-Weinberg equilibrium of the reported magnitude. However, we found no evidence of an excess of homozygosity in our schizophrenic patients. This seems to indicate that homozygosity for the Gly9/Ser9 polymorphism at the DRD3 locus is unlikely to confer susceptibility to schizophrenia in the German population. This held true whether the psychiatric diagnoses in the affected relatives of the patient samples was established by the family history or family interview method.
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PMID:Dopamine D3 receptor Gly9/Ser9 polymorphism and schizophrenia: no increased frequency of homozygosity in German familial cases. 879 8

Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied.
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PMID:Association study of dopamine D3 receptor gene and schizophrenia. 882 96

Crocq et al. [1992: J Med Genet 29:858-860] reported the existence of an association between schizophrenia and homozygosity of a BalI polymorphism in the first exon of the dopamine D3 receptor (DRD3) gene. In response to this report, further studies were conducted; however, these studies yielded conflicting results. In the present study, we examined 100 unrelated Japanese schizophrenics and 100 normal controls to determine any association between this polymorphism and schizophrenia. Results suggest that neither allele nor genotype frequencies of the DRD3 gene in the schizophrenics as a whole are significantly different from those of the controls. Further, we found no association between any allele or genotype and any clinical subtype based on family history of schizophrenia and age-at-onset. A significantly high frequency of homozygosity of a dopamine D3 receptor gene allele was not observed in the schizophrenics as a whole, or in clinical subtypes. Our results suggest that an association between the dopamine D3 receptor gene and schizophrenia is unlikely to exist.
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PMID:Association study between schizophrenia and dopamine D3 receptor gene polymorphism. 883 4

Association of the dopamine D3 receptor gene (DRD3) and schizophrenia was examined in unrelated Israeli and Italian schizophrenic patients and ethnically matched normal control subjects. In the combined sample, there was a significant excess of DRD3 allele 2 among the schizophrenic patients (chi2 = 4.70, d.f. 1, p = 0.03). Comparison of genotype frequencies revealed an excess of the 2-2 genotype in the combined schizophrenic sample (chi2 = 8.30, d.f. 1, p = 0.01) and in the non-Ashkenazi Israeli schizophrenics alone (chi2 = 5.70, d.f. 2, p = 0.05). DRD3 2-2 genotype conferred a significantly increased risk of schizophrenia (chi2 = 8.21, d.f. 1, p = 0.004; OR = 2.87, CI 95% = 1.36-5.76) in the combined sample and in the non-Ashkenazi Israeli schizophrenics (chi2 = 7.22, d.f. 1, p = 0.04; OR = 7.22, CI 95% = 1.04-24.83). In the combined and Italian samples, allele 2 was associated with early age of onset as was the 2-2 genotype in the combined sample and non-Ashkenazi group. The 2-2 genotype was associated with poor response to neuroleptics, particularly in the non-Ashkenazi, Israeli schizophrenics. The possibility that DRD3 or a locus in linkage disequilibrium with it may play a role in the transmission of schizophrenia, is considered in relation to previous positive and negative reports.
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PMID:Evidence for an association between the dopamine D3 receptor gene DRD3 and schizophrenia. 901 73


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