| 1 | World J. Biol. Psychiatry 2008 -1 9: 225-30 |
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| PMID | 17853297 |
| Title | Complement C4B protein in schizophrenia. |
| Abstract | Partial and/or complete deficiency of the complement protein C4 is associated with autoimmune and infectious diseases. Infectious or autoimmune processes may have a role in schizophrenia. Previous reports suggest abnormalities in the complement C4B isotype in schizophrenia and other mental disorders. We assessed C4A and C4B isotypes and serum C4B protein concentration in Armenian schizophrenic patients. Although there was no difference in frequency of C4BQ0, C4B serum protein level was significantly decreased in the schizophrenic patients compared with healthy controls. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | World J. Biol. Psychiatry 2008 -1 9: 225-30 |
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| PMID | 17853297 |
| Title | Complement C4B protein in schizophrenia. |
| Abstract | Partial and/or complete deficiency of the complement protein C4 is associated with autoimmune and infectious diseases. Infectious or autoimmune processes may have a role in schizophrenia. Previous reports suggest abnormalities in the complement C4B isotype in schizophrenia and other mental disorders. We assessed C4A and C4B isotypes and serum C4B protein concentration in Armenian schizophrenic patients. Although there was no difference in frequency of C4BQ0, C4B serum protein level was significantly decreased in the schizophrenic patients compared with healthy controls. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | J. Hum. Genet. 2010 May 55: 285-92 |
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| PMID | 20339380 |
| Title | An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes. |
| Abstract | schizophrenia is a highly complex inheritable disease characterized by numerous genetic susceptibility elements, each contributing a modest increase in risk for the disease. Although numerous linkage or association studies have identified a large set of schizophrenia-associated loci, many are controversial. In addition, only a small portion of these loci overlaps with the large cumulative pool of genes that have shown changes of expression in schizophrenia. Here, we applied a genomic gene-function approach to identify susceptibility loci that show direct effect on gene expression, leading to functional abnormalities in schizophrenia. We carried out an integrated analysis by cross-examination of the literature-based susceptibility loci with the schizophrenia-associated expression gene list obtained from our previous microarray study (Journal of Human Genetics (2009) 54: 665-75) using bioinformatic tools, followed by confirmation of gene expression changes using qPCR. We found nine genes (CHGB, SLC18A2, SLC25A27, ESD, C4A/C4B, TCP1, CHL1 and CTNNA2) demonstrate gene-function correlation involving: synapse and neurotransmission; energy metabolism and defense mechanisms; and molecular chaperone and cytoskeleton. Our findings further support the roles of these genes in genetic influence and functional consequences on the development of schizophrenia. It is interesting to note that four of the nine genes are located on chromosome 6, suggesting a special chromosomal vulnerability in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | J Psychiatr Res 2012 Nov 46: 1464-74 |
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| PMID | 22954356 |
| Title | A combined analysis of microarray gene expression studies of the human prefrontal cortex identifies genes implicated in schizophrenia. |
| Abstract | Small cohort sizes and modest levels of gene expression changes in brain tissue have plagued the statistical approaches employed in microarray studies investigating the mechanism of schizophrenia. To combat these problems a combined analysis of six prior microarray studies was performed to facilitate the robust statistical analysis of gene expression data from the dorsolateral prefrontal cortex of 107 patients with schizophrenia and 118 healthy subjects. Multivariate permutation tests identified 144 genes that were differentially expressed between schizophrenia and control groups. Seventy of these genes were identified as differentially expressed in at least one component microarray study but none of these individual studies had the power to identify the remaining 74 genes, demonstrating the utility of a combined approach. Gene ontology terms and biological pathways that were significantly enriched for differentially expressed genes were related to neuronal cell-cell signaling, mesenchymal induction, and mitogen-activated protein kinase signaling, which have all previously been associated with the etiopathogenesis of schizophrenia. The differential expression of BAG3, C4B, EGR1, MT1X, NEUROD6, SST and S100A8 was confirmed by real-time quantitative PCR in an independent cohort using postmortem human prefrontal cortex samples. Comparison of gene expression between schizophrenic subjects with and without detectable levels of antipsychotics in their blood suggests that the modulation of MT1X and S100A8 may be the result of drug exposure. In conclusion, this combined analysis has resulted in a statistically robust identification of genes whose dysregulation may contribute to the mechanism of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | J Psychiatr Res 2012 Nov 46: 1464-74 |
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| PMID | 22954356 |
| Title | A combined analysis of microarray gene expression studies of the human prefrontal cortex identifies genes implicated in schizophrenia. |
| Abstract | Small cohort sizes and modest levels of gene expression changes in brain tissue have plagued the statistical approaches employed in microarray studies investigating the mechanism of schizophrenia. To combat these problems a combined analysis of six prior microarray studies was performed to facilitate the robust statistical analysis of gene expression data from the dorsolateral prefrontal cortex of 107 patients with schizophrenia and 118 healthy subjects. Multivariate permutation tests identified 144 genes that were differentially expressed between schizophrenia and control groups. Seventy of these genes were identified as differentially expressed in at least one component microarray study but none of these individual studies had the power to identify the remaining 74 genes, demonstrating the utility of a combined approach. Gene ontology terms and biological pathways that were significantly enriched for differentially expressed genes were related to neuronal cell-cell signaling, mesenchymal induction, and mitogen-activated protein kinase signaling, which have all previously been associated with the etiopathogenesis of schizophrenia. The differential expression of BAG3, C4B, EGR1, MT1X, NEUROD6, SST and S100A8 was confirmed by real-time quantitative PCR in an independent cohort using postmortem human prefrontal cortex samples. Comparison of gene expression between schizophrenic subjects with and without detectable levels of antipsychotics in their blood suggests that the modulation of MT1X and S100A8 may be the result of drug exposure. In conclusion, this combined analysis has resulted in a statistically robust identification of genes whose dysregulation may contribute to the mechanism of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Neurosci. Lett. 2015 Mar 590: 189-92 |
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| PMID | 25660618 |
| Title | An evaluation of association between common variants in C4BPB/C4BPA genes and schizophrenia. |
| Abstract | Epidemiological studies have indicated that both maternal bacterial and viral infections during pregnancy increase the risk of schizophrenia among offspring, but to date there is not clear explanation for this increased risk. Previously, the decreased C4B-binding protein (C4BP), a potent circulating soluble inhibitor of the classical and lectin pathways of complement, was reported to be associated with risk of schizophrenia. Here, we analyzed 4 common single nucleotide polymorphisms (SNPs) of C4BPB and 5 SNPs of C4BPA in a group of 556 schizophrenia patients and a matched group of 610 healthy controls to see if the genes C4BPB and C4BPA, which encode C4BP, may confer a susceptibility to schizophrenia. Comparing the genotype and allele frequencies of those SNPs between cases and controls, we found no association between the C4BPB/C4BPA variants and schizophrenia. Our results provided preliminary evidence that C4BPB/C4BPA may not confer susceptibility to schizophrenia among Han Chinese. Further genetic studies from large-scale population are required to obtain more conclusive results. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Nature 2016 Feb 530: 177-83 |
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| PMID | 26814963 |
| Title | Schizophrenia risk from complex variation of complement component 4. |
| Abstract | schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |