| 1 | Proteomics 2012 Jun 12: 1815-29 |
|---|---|
| PMID | 22623148 |
| Title | Roles of interferon-gamma and its target genes in schizophrenia: Proteomics-based reverse genetics from mouse to human. |
| Abstract | A decreased production of interferon gamma (IFNG) has been observed in acuteschizophrenia。In order to explore the possible relationship betweenIFNGandschizophrenia, we attempted to analyze the differentially expressed proteins in the brains of interferon-gamma knockout (IFNG-KO) mice. Five upregulated and five downregulated proteins were identified with 2D gels and MALDI-TOF/TOF MS analyses inIFNG-KO mouse brain. Of the identified proteins, we focused on creatine kinase brain (CKB) and triose phosphate isomerase 1 (TPI1). Consistent with the proteomic data, reverse transcriptase-mediated PCR, immunoblotting, and immunohistochemistry analyses confirmed that the levels of gene expressions of Ckb and Tpi1 were downregulated and upregulated, respectively. When we analyzed the genetic polymorphisms of the single nucleotide polymorphisms (SNPs) of their human orthologous genes in a Korean population, the promoter SNPs of CKB and TPI1 were weakly associated withschizophrenia。In addition,IFNGpolymorphisms were associated withschizophrenia。These results suggest thatIFNGand proteins affected byIFNG可能在schizophrenia。 |
| SCZ关键字 | schizophrenia |
| 2 | Mol. Biol. Rep. 2013 Oct 40: 5607-14 |
| PMID | 24065520 |
| Title | 基因变异在转变增长前沿空中管制官tor-? gene (TGFB1) affect susceptibility to schizophrenia. |
| Abstract | Immense body of evidence indicates that dysfunction of immune system is implicated in the etiology ofschizophrenia。免疫理论schizophreniais supported by alterations in cytokine profile in the brain and peripheral blood. Given the strong genetic background ofschizophrenia, it might be assumed that aberrant production of cytokines might be the consequence of genetic factors. This study aimed at investigating the association betweenschizophreniasusceptibility and selected functional polymorphisms in genes encoding cytokines including: interleukin-2 (IL2 -330T>G, rs2069756), interleukin-6 (IL-6 -174G>C, rs1800795), interferon-? (IFNG+874T>A, rs2430561) as well as for the first time transforming growth factor-?1 (TGFB1 +869T>C, rs1800470 and +916G>C, rs1800471). We recruited 151 subjects withschizophreniaand 279 controls. There was a significant difference in the genotype distribution and allelic frequency of the TGFB1 +869T>C between patients withschizophrenia和健康对照（p <0.05）。风险schizophreniawas more than two-fold higher in carriers of T allele (CT+TT genotypes) than individuals with CC genotype. Given documented gender differences in incidence ofschizophrenia, we conducted separate analyses of male and female participants. We have shown that the association was significant in females, while in males it reached a trend toward statistical significance. To the best of our knowledge, it is the first report showing the association between TGFB1 +869T>C polymorphism andschizophrenia。 |
| SCZ关键字 | schizophrenia |
| 3 | J Neuroinflammation 2016 -1 13: 105 |
| PMID | 27177030 |
| Title | Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia. |
| Abstract | Inschizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger the changes that lead to impaired neuronal functions. Cytokines being the key regulators of immune/inflammatory reactions are also known to influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. Therefore, functional polymorphisms in cytokine genes may result in imbalances in the pro- and anti-inflammatory cytokine production. We screened polymorphisms in pro- and anti-inflammatory cytokine genes using a case-control association study in a South Indian population. The role of allele, genotype, haplotype, and diplotypes of these cytokine genes and their epistatic interactions were assessed in contributing to the risk of developingschizophrenia。Meta-analysis for the reported associations was also monitored for global significance. IL1ARS1800587，IL6RS1800796，TNFARS361525中的促炎细胞因子基因多态性和IFNGrs2069718 were associated withschizophrenia。The study also provides significant evidence for strong epistatic interactions among pro-inflammatory cytokine genes IL6 andIFNGin the development ofschizophrenia。In silico analysis suggested that associated risk variants were indicative of altered transcriptional activity with higher production of IL1?, IL-6, TNF-?, and IFN-? cytokines. Meta-analysis indicated heterogeneity among study population while IL1Ars1800587 was found to be globally significant. 重要的是要确定可以通过环境扩增的炎症反应的性质，以影响Th1反应或TH2响应。研究中相关的功能变异涉及增加的表达，从而导致促炎性细胞因子IL-1？，IL-6，TNF-？和IFN-？的产生较高。免疫应激源与这些促炎细胞因子的这些高产量等位基因的相互作用可能表明，即使阈值也可能足以诱导对心理社会和环境压力源的慢性影响，这可能会导致可能导致的发展和发病机理schizophrenia。Understanding environmental factors that influence the expression of these pro-inflammatory cytokine genes or their interaction can possibly help in dissecting the phenotypic variation and therapeutic response to antipsychotics inschizophrenia。 |
| SCZ关键字 | schizophrenia |