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)

Neurodevelopmental abnormalities have been reported in studies on the pathogenesis of schizophrenia. The Wnt-signaling pathway has been implicated in a variety of processes in neurodevelopment, and the frizzled proteins have been identified as receptors for Wnt ligands. Of the frizzled proteins, frizzled-3 (FZD3) is required for formation of the neural crest and for development of major fiber tracts in the CNS. The human FZD3 gene is located on chromosome 8p21, a positive linkage locus for schizophrenia. We analyzed polymorphisms of the FZD3 gene in patients with schizophrenia and control subjects in the Japanese population. We found a significant association between schizophrenia and the FZD3 gene in single nucleotide polymorphisms and haplotype analyses. Our data suggest that dysregulation of the Wnt-signaling pathway may be involved in the susceptibility to schizophrenia.
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PMID:The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia. 1464 36

In recent studies, the frizzled-3 (FZD3) locus was found to be associated with schizophrenia in both Japanese and Chinese populations. To validate the initial finding, we detected three single nucleotide polymorphisms (SNPs) present in a 10-kb segment of DNA at the FZD3 locus, as described in a previous study with a Chinese population. We totally recruited 120 British family trios consisting of fathers, mothers and affected offspring with schizophrenia. The transmission disequilibrium test (TDT) did not show allelic association between these three SNPs and schizophrenia. The 3-SNP haplotype system was composed of only 3 individual haplotypes among the 120 family trios and these 3 SNPs were mainly carried by two distinct haplotypes, suggesting that these 3 SNPs may result from a single founding event in history. No association was shown between the 3-SNP haplotypes and schizophrenia. The present results imply that the FZD3 gene is less evolutionary in the British population than in the Chinese population. This may be a possible reason for the failure to replicate the FZD3 finding with the British sample.
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PMID:Lack of a genetic association between the frizzled-3 gene and schizophrenia in a British population. 1528 46

Two research groups have recently reported a significant association between schizophrenia and genetic variants of Frizzled-3 (FZD3) gene. We examined a possible association in a Japanese sample of schizophrenia, bipolar disorder, unipolar depression and controls with four single nucleotide polymorphisms (SNPs), tested in previous reports. We failed to find significant association in the four SNPs or haplotype analysis. The FZD3 gene might not play a role in conferring susceptibility to major psychosis in our sample.
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PMID:Association study of the frizzled-3 (FZD3) gene with schizophrenia and mood disorders. 1565 45

Chromosome 8p22-p11 has been identified as a locus for schizophrenia in several genome-wide scans, which has been confirmed by meta-analysis of published linkage data. It appears to be 1 of the most robust linkage findings in psychosis. Several attempts have been made to identify the underlying genetic variation that gives rise to this linkage peak, including systematic fine mapping using extended Icelandic pedigrees that have identified an associated haplotype (HAP(ICE)) in the gene neuregulin 1, also known as heuregulin, glial growth factor, NDF43, and ARIA. Neuregulin 1 (NRG1) is a plausible susceptibility gene because of its involvement in neurodevelopment, regulation of glutamate and other neurotransmitter receptor expression, and synaptic plasticity. Encouragingly, this finding was quickly and directly replicated in a Scottish case-control sample by the same investigators with the same approximately 300 kb associated haplotype. Although in Caucasian populations subsequent attempts at replication of this finding have been difficult to interpret, and no individual functional or causative genetic variants have yet been identified, a summary of HAP(ICE) association results in about 4,500 subjects is consistent with a small (odds ratio approximately 1.5) but significant effect of this haplotype on schizophrenia risk. In Chinese Han populations, where HAP(ICE) is not found, there is good evidence from several studies of association with other markers in the same region. Overall, there is convincing but not yet compelling evidence for a role for NRG1 in susceptibility to schizophrenia. Other genes from this region have also been implicated in schizophrenia, not by systematic mapping but by positional candidate gene analysis; these include MSTP131, frizzled-3, and the calcineurin A gamma subunit gene. Not only are these alternative explanations for the linkage seen between chromosome 8p and schizophrenia, but it is equally possible that there is more than 1 susceptibility gene at this locus.
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PMID:Association between the neuregulin 1 gene and schizophrenia: a systematic review. 1608 9

The neurodevelopmental hypothesis offers a promising approach through which to explore the pathogenesis of schizophrenia. Human Frizzled-3 protein is one of the major components of the Wnt signaling pathway and plays a crucial role in regulating early neurodevelopmental processes. Therefore, the human Frizzled homolog 3 (FZD3) gene, which encodes this protein, may be an excellent candidate gene for association studies of schizophrenia. To replicate the previously reported positive association between FZD3 and schizophrenia in Han Chinese and Japanese populations, we genotyped two single nucleotide polymorphism (SNP) markers of FZD3 in 241 unrelated schizophrenic patients and 192 control subjects. Fisher's exact test was used to compare the genotypic and allelic frequencies in the two groups. In addition, to integrate and evaluate the accumulated evidence published to date, we performed a meta-analysis on the published data, including our own. No evidence was found to support the association between either of the investigated SNP markers and schizophrenia in a Korean population. Moreover, the meta-analytic result did not support the association between several commonly investigated markers in FZD3 and schizophrenia. Failure to replicate previous positive association results could reflect various theoretical factors. Therefore, other sources of error have to be ruled out before coming to a conclusion. In the case of FZD3, it seems that repeated failures to replicate the original results by several independent research groups combine to provide evidence against an association between FZD3 and schizophrenia. Other candidate genes involved in early neurodevelopmental processes may deserve further investigation.
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PMID:Investigation of genetic association between human Frizzled homolog 3 gene (FZD3) and schizophrenia: results in a Korean population and evidence from meta-analysis. 1670 63

Clozapine has markedly superior clinical properties compared to other antipsychotic drugs but the side effects of agranulocytosis, weight gain and diabetes limit its use. The reason why clozapine is more effective is not well understood. We studied messenger RNA (mRNA) gene expression in the mouse brain to identify pathways changed by clozapine compared to those changed by haloperidol so that we could identify which changes were specific to clozapine. Data interpretation was performed using an over-representation analysis (ORA) of gene ontology (GO), pathways and gene-by-gene differences. Clozapine significantly changed gene expression in pathways related to neuronal growth and differentiation to a greater extent than haloperidol; including the microtubule-associated protein kinase (MAPK) signalling and GO terms related to axonogenesis and neuroblast proliferation. Several genes implicated genetically or functionally in schizophrenia such as frizzled homolog 3 (FZD3), U2AF homology motif kinase 1 (UHMK1), pericentriolar material 1 (PCM1) and brain-derived neurotrophic factor (BDNF) were changed by clozapine but not by haloperidol. Furthermore, when compared to untreated controls clozapine specifically regulated transcripts related to the glutamate system, microtubule function, presynaptic proteins and pathways associated with synaptic transmission such as clathrin cage assembly. Compared to untreated controls haloperidol modulated expression of neurotoxic and apoptotic responses such as NF-kappa B and caspase pathways, whilst clozapine did not. Pathways involving lipid and carbohydrate metabolism and appetite regulation were also more affected by clozapine than by haloperidol.
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PMID:A gene expression and systems pathway analysis of the effects of clozapine compared to haloperidol in the mouse brain implicates susceptibility genes for schizophrenia. 2276 72