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)

Although population genetic studies have long confirmed the genetic vulnerability of schizophrenia,ongoing advances in molecular genetic technology and biostatistic analysis are only now making it possible to search for the susceptibility gene of the disease. This article reviewed some of the recent findings in this area: (1) The heritability of schizophrenia is estimated around 60%-80%. The phenotype differentiation is based on standard diagnostic scales and symptom rating scales. (2) The two main approaches to finding the genes that influence the disorder are now genomic scan and candidate gene detection. Affected sib-pair (ASP) method and transmission disequilibrium test(TDT) are considered promising analyses. (3) The positive candidate regions with some independent replicable reports concentrated on 6p, 22q and 8p. Positive findings of candidate gene research involved 5-HT2A receptor, DRD3, NT-3, etc. Further directions to identify the susceptibility genes include: Applying more precise instruments to define clinical phenotype of the disease. Application of proper biological markers such as electrophysiologic parameters and brain imaging will be a prospective approach. Using larger sample to increase statistic power and developing more powerful statistic analysis, and performing advanced molecular genetic technique such as DNA pooling, DNA chips, genomic mismatch scanning (GMS), representational difference analysis(RDA), comparative genomic hybridization(CGH) and two-dimensional DNA typing methods will also facilitate this research area to greater perspective.
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PMID:[Progress in the studies on the molecular genetics of schizophrenia]. 1111 Sep 86

Several recent meta-analyses appear to show a weak but significant effect of both forms of the gly/ser DRD3 polymorphism in conferring risk for schizophrenia. Since most studies have employed the artifact-prone case-control design, we thought it worthwhile to examine the role of this polymorphism using a robust family-based strategy in an ethnic group not previously systematically studied in psychiatric genetics, Palestinian Arabs. We failed to obtain any evidence in 129 Palestinian triads, using the haplotype relative risk (allele frequency: Pearson chi-square = 0.009, P > 0.1, df = 1, n = 258 alleles) or transmission disequilibrium test design (chi-square = 0.38, P > 0.1, n = 86 families) for association/linkage (or increased homozygosity) of the DRD3 Bal I polymorphism to schizophrenia in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:778-780, 2000.
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PMID:No association between the dopamine D3 receptor Bal I polymorphism and schizophrenia in a family-based study of a Palestinian Arab population. 1112 Nov 80

Tardive dyskinesia (TD) is characterized by involuntary movements predominantly in the orofacial region and develops in approximately 20% of patients during long-term treatment with typical antipsychotics. The high prevalence of TD and its disabling and potentially irreversible clinical course is an important shortcoming for treatment with typical antipsychotics. The studies presented in this article evaluate the role of single nucleotide polymorphisms in dopamine D3 receptor (DRD3) and CYP1A2 genes for propensity to develop TD in patients with schizophrenia. In theory, a combined pharmacogenetic analysis of pharmacokinetic and pharmacodynamic targets for antipsychotics should improve our ability to identify subpopulations that differ in drug safety profile. This information may in turn contribute to the design of more efficient clinical trials and thus expedite the development and regulatory approval of newer antipsychotic compounds.
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PMID:Pharmacogenetic assessment of antipsychotic-induced movement disorders: contribution of the dopamine D3 receptor and cytochrome P450 1A2 genes. 1117 71

This study was undertaken to re-examine whether homozygosity for the Gly-9 variant (allele 2) of the dopamine D3 receptor gene (DRD3) is associated with increased risk for tardive dyskinesia (TD) in schizophrenic patients. Seventy-one antipsychotic-treated subjects with schizophrenia from Newcastle upon Tyne, UK, were genotyped for the presence of allele 1 (Ser-9) and allele 2 (Gly-9) of the dopamine D3 receptor (DRD3) Ser-9-Gly polymorphism. Among 32 patients with TD, 7 subjects (22 %) were homozygous for the Gly-9 variant (2-2 genotype), whereas 4 out of 39 patients (10 %) without TD had this genotype. The non-significant tendency in this sample towards an over-representation of allele 2 and the 2-2 genotype among schizophrenic patients with TD is in line with our initial report as well as recent studies by others, indicating that the Gly-9 allele of DRD3 may be a susceptibility factor for the development of TD in neuroleptic-treated individuals with schizophrenia. There are, however, some recent non-supportive reports, and since the trend in our present study failed to reach statistical significance, further studies on larger samples and future meta-analysis may be necessary to establish the role of the DRD3 in the pathogenesis of TD.
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PMID:Homozygosity for the Gly-9 variant of the dopamine D3 receptor and risk for tardive dyskinesia in schizophrenic patients. 1134 80

Clinical studies have shown that there is a genetic contribution to the pathogenesis of schizophrenia. The molecular mechanisms of effective antipsychotic drugs and recent advances in neural development suggest that several dopamine receptor, serotonin receptor and neurotrophic factor genes might be involved in the disorder. In this study, we assessed the associations between schizophrenia and polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3), the serotonin 2A receptor (5HTR2A), the brain-derived neurotrophic factor (BDNF), the ciliary neurotrophic factor (CNTF) and the neurotrophin-3 (NT-3) genes. Our results suggest that the polymorphisms at the DRD3, 5HTR2A, CNTF and BDNF gene loci are unlikely to make our sample more genetically susceptible to schizophrenia. However, we found significant differences in microsatellite allele frequencies between schizophrenic and control groups for DRD2 in the whole sample and for DRD2 and NT-3 only in women. Therefore, clinical differences in the presentation of schizophrenia between gender might be related to genetic factors.
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PMID:Association study of schizophrenia with polymorphisms at six candidate genes. 1134 65

Bipolar disorder is a major psychiatric illness that has evidence for a significant genetic contribution toward its development. In recent years, the BalI RFLP (restriction fragment length polymorphism) in the dopamine D3 receptor gene has been examined as a possible susceptibility factor for both schizophrenia and bipolar disorder. While analysis in schizophrenia has produced examples of increased homozygosity in patients, less encouraging results have been found for bipolar disorder. Recently, however, a family-based association study has found a significant excess of allele 1 and allele 1-containing genotypes in transmitted alleles to bipolar probands over nontransmitted controls. In a large bipolar case control sample (n = 454), we have been unable to replicate the family-based association study (chi-square = 0.137, P = 0.71, 1 df) or detect an effect similar to the positive homozygosity findings in schizophrenia (chi-square = 0.463, P = 0.50, 1 df). A meta-analysis of previous association studies also revealed no difference in allele distributions between bipolar patients and controls for this polymorphism in ethnically homogeneous samples (odds ratio, OR, = 1.04; P = 0.60; 95% confidence interval, CI, = 0.89-1.20). In view of this evidence, we conclude that variation at the BalI RFLP is not an important factor influencing the susceptibility to bipolar disorder. It remains possible, however, that other sequence variations within the DRD3 gene could play a role.
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PMID:Allelic variation of a BalI polymorphism in the DRD3 gene does not influence susceptibility to bipolar disorder: results of analysis and meta-analysis. 1137 41

Epidemiological studies have shown a lower prevalence of tardive dyskinesia (TD) among Chinese psychiatric patients compared to Caucasian and Black patient populations. It has been hypothesized that pharmacogenetic factors may underlie this cross-cultural difference. Due to the important implications of the dopamine D3 receptor gene (DRD3) in motor control, we investigated the frequency of polymorphic serine (ser) to glycine (gly) substitution of the gene DRD3 in Chinese schizophrenic patients. The sample size consisted of 65 patients with TD and 66 without TD. Patients were assessed for the severity of TD, the presence of akathisia and parkinsonian symptoms and were subsequently genotyped. We found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia in Chinese patients with schizophrenia.
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PMID:Dopamine D3 receptor gene and tardive dyskinesia in Chinese schizophrenic patients. 1147 19

Altered dopamine neurotransmission and eye movement disturbances have been implicated in the pathogenic process of schizophrenia. So far, molecular genetic studies have shown little association between schizophrenia and polymorphism of any dopamine receptor or transporter genes except for some findings concerning D3 receptor (DRD3) gene. Eye movement disturbances occur in a majority of patients with schizophrenia and in a proportion of their first-degree relatives and they have been suggested as a phenotypic marker in genetic studies of this illness. Here we report an association between the Ser9Gly polymorphism of the DRD3 gene and the intensity of eye movement disturbances (fixation and smooth pursuit) observed in 119 schizophrenic patients and in 94 unrelated healthy control subjects. In schizophrenic patients, the mean intensity of both kinds of eye movement disturbances was highest in individuals with the Ser-Ser genotype, significantly lower in Ser-Gly and lowest in the Gly-Gly genotype. The Ser-Ser genotype was more prevalent in patients with a higher intensity of both fixation (58.1 vs 23.9% P < 0.001) and smooth pursuit disturbances (52.3 vs 25.8%, P < 0.02) and the Ser-Gly genotype frequency was lower in patients with higher fixation disturbances (37.0 vs 60.9%, P < 0.02). In control subjects, the genotype frequency Ser-Ser was higher in subjects with any degree of eye movement disturbances compared to subjects without such disturbances both for fixation and smooth pursuit performance (81.0 vs 50.7%, P < 0.05 and 79.2 vs 50.0%, P < 0.05, respectively). In control subjects the frequency of Ser-Gly was lower in the first group, for either fixation or smooth pursuit, compared to normal performers (9.5 vs 43.8%, P < 0.01 and 8.3 vs 45.7, P < 0.005, respectively). We suggest that the DRD3 Ser9Gly polymorphism may be a contributing factor to the performance of eye movements used as a phenotypic marker of schizophrenia.
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PMID:Dopamine D3 receptor (DRD3) gene polymorphism is associated with the intensity of eye movement disturbances in schizophrenic patients and healthy subjects. 1167 1

The genetic etiology of schizophrenia, a common and debilitating psychiatric disorder, is supported by a wealth of data. Review of the current findings suggests that considerable progress has been made in recent years, with a number of chromosomal regions consistently implicated by linkage analysis. Three groups have shown linkage to 1q21-22 using similar models, with HLOD scores of 6.5, 3.2, and 2.4. Other replicated loci include 13q32 that has been implicated by two independent groups with significant HLOD scores (4.42) or NPL values (4.18), and 5pl4.1-13.1, 5q21-33, 8p2l-22, and 10p11-15, each of which have been reported as suggestive by at least three separate groups. Different studies have also replicated evidence for a modest number of candidate genes that were not ascertained through linkage. Of these, the greatest support exists for the DRD3 (3q13.3), HTR2A (13q14.2), and CHRNA7 (15q13-q14) genes. The refinement of phenotypes, the use of endophenotypes, reduction of heterogeneity, and extensive genetic mapping have all contributed to this progress. The rapid expansion of information from the human genome project will likely further accelerate this progress and assist in the discovery of susceptibility genes for schizophrenia. A greater understanding of disease mechanisms and the application of pharmacogenetics should also lead to improvements in therapeutic interventions.
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PMID:Recent advances in the genetics of schizophrenia. 1191 47

The dopamine D(3) receptor gene (DRD3) is a candidate for a number of psychiatric conditions including schizophrenia, bipolar disorder and alcohol and drug abuse. Previous studies have reported associations between polymorphisms in DRD3 and these disorders, but these findings may have reflected linkage disequilibrium with pathogenic variants that are further upstream. We have isolated and sequenced approximately 9 kb of genomic sequence upstream of the human DRD3 translational start site. Using 5' RACE, we have identified within this region three additional exons and two putative promoter regions which show promoter activity in three different cell lines. A 5' UTR identified only in lymphoblasts is spread over three exons and is 353 bp long. A second 5' UTR, found in adult and fetal brain, lymphocytes, kidney and placenta is spread over two exons and is 516 bp long. A 260-bp sequence within this 9 kb corresponds to a previously reported EST, but corresponding mRNA could not be found in the tissues above. The EST, 5' UTRs and putative promoter regions have been analysed for polymorphisms, revealing 10 single nucleotide polymorphisms, seven of which were tested for association in a large sample of unrelated patients with schizophrenia and matched controls. No associations were observed with schizophrenia. In addition we failed to replicate previous findings of association with homozygosity of the Ser9Gly variant. The results from this study imply that neither the coding nor the regulatory region of DRD3 plays a major role in predisposition to schizophrenia.
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PMID:Characterisation, mutation detection, and association analysis of alternative promoters and 5' UTRs of the human dopamine D3 receptor gene in schizophrenia. 1208 67


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