| 1 | 地中海,假设2006-1 67: 427-8 |
|---|---|
| PMID | 16644139 |
| 标题 | 精神分裂症和癌症风险：CCR5-DELTA 32趋化因子受体基因突变可以起作用吗？ |
| Abstract | -1 |
| SCZ关键字 | schizophrenia |
| 2 | Am J Psychiatry 2006 Mar 163: 507-11 |
| PMID | 16513874 |
| 标题 | Association between the CCR5 32-bp deletion allele and late onset of schizophrenia. |
| Abstract | The 32-bp deletion allele in chemokine receptorCCR5has been associated with several immune-mediated diseases and might be implicated inschizophreniaas well. The authors genotyped DNA samples from 268schizophreniapatients and 323 healthy subjects. Age at first admission to a psychiatric hospital department served as a measure of disease onset. Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher age at first admission. After age at first admission was analyzed as a continuous variable, it was dichotomized using 40 years as the cutoff. With this approach the authors found that genotype distributions of patients with age at first admission above the cutoff (possible cases of late-onsetschizophrenia）和健康受试者的差异很大。这反映在患者亚组中缺失等位基因的频率增加中。在40岁以下和40岁以上的初次入院时年龄的患者在基因型和等位基因的分布方面显着差异，而后者的患者亚组中缺失等位基因的分量过高。 These findings suggest that theCCR532-bp deletion allele is a susceptibility factor forschizophrenia发作迟到。或者CCR532-bp deletion allele may act as a modifier by delaying the onset ofschizophreniawithout affecting the disease susceptibility. |
| SCZ关键字 | schizophrenia |
| 3 | Schizophr Bull 2009 Nov 35: 1163-82 |
| PMID | 18552348 |
| 标题 | Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii. |
| Abstract | Many genes implicated inschizophreniacan be related to glutamatergic transmission and neuroplasticity, oligodendrocyte function, and other families clearly related to neurobiology andschizophreniaphenotypes. Others appear rather to be involved in the life cycles of the pathogens implicated in the disease. For example, aspartylglucosaminidase (AGA), PLA2, SIAT8B, GALNT7, or B3GAT1 metabolize chemical ligands to which the influenza virus, herpes simplex, cytomegalovirus (CMV), rubella, or Toxoplasma gondii bind. The epidermal growth factor receptor (EGR/EGFR) is used by the CMV to gain entry to cells, and a CMV gene codes for an interleukin (IL-10) mimic that binds the host cognate receptor, IL10R. The fibroblast growth factor receptor (FGFR1) is used by herpes simplex. KPNA3 and RANBP5 control the nuclear import of the influenza virus. Disrupted inschizophrenia1 (DISC1)控制的微管网络used by viruses as a route to the nucleus, while DTNBP1, MUTED, and BLOC1S3 regulate endosomal to lysosomal routing that is also important in viral traffic. Neuregulin 1 activates ERBB receptors releasing a factor, EBP1, known to inhibit the influenza virus transcriptase. Other viral or bacterial components bind to genes or proteins encoded by CALR, FEZ1, FYN, HSPA1B, IL2, HTR2A, KPNA3, MED12, MED15, MICB, NQO2, PAX6, PIK3C3, RANBP5, or TP53, while the cerebral infectivity of the herpes simplex virus is modified by Apolipoprotein E (APOE). Genes encoding for proteins related to the innate immune response, including cytokine related (CCR5, CSF2RA, CSF2RB, IL1B, IL1RN, IL2, IL3, IL3RA, IL4, IL10, IL10RA, IL18RAP, lymphotoxin-alpha, tumor necrosis factor alpha [TNF]), human leukocyte antigen (HLA) antigens (HLA-A10, HLA-B, HLA-DRB1), and genes involved in antigen processing (angiotensin-converting enzyme and tripeptidyl peptidase 2) are all concerned with defense against invading pathogens. Human microRNAs (Hsa-mir-198 and Hsa-mir-206) are predicted to bind to influenza, rubella, or poliovirus genes. Certain genes associated withschizophrenia, including those also concerned with neurophysiology, are intimately related to the life cycles of the pathogens implicated in the disease. Several genes may affect pathogen virulence, while the pathogens in turn may affect genes and processes relevant to the neurophysiology ofschizophrenia. For such genes, the strength of association in genetic studies is likely to be conditioned by the presence of the pathogen, which varies in different populations at different times, a factor that may explain the heterogeneity that plagues such studies. This scenario also suggests that drugs or vaccines designed to eliminate the pathogens that so clearly interact withschizophreniasusceptibility genes could have a dramatic effect on the incidence of the disease. |
| SCZ关键字 | schizophrenia |
| 4 | Transl Psychiatry 2014 -1 4: e406 |
| PMID | 24984193 |
| 标题 | Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia. |
| Abstract | We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from eitherschizophrenia(SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulatedCCR5(P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgf? (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity. |
| SCZ关键字 | schizophrenia |
| 5 | Schizophr. Res. 2015 Feb 161: 215-21 |
| PMID | 25487697 |
| 标题 | 躁郁症和精神分裂症之间的先天免疫反应差异失调。 |
| Abstract | schizophrenia(SZ) and bipolar disorder (BD) are severe psychiatric conditions with a neurodevelopmental component. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. Also, image studies provide evidence for a shared neurobiological basis, contributing to a dimensional diagnostic approach. This study aimed to identify the molecular mechanisms that differentiate SZ and BD patients from health controls but also that distinguish both from health individuals. Comparison of gene expression profiling in post-mortem brains of both disorders and health controls (30 cases), followed by a further comparison between 29 BD and 29 SZ revealed 28 differentially expressed genes. These genes were used in co-expression analysesthat revealed the pairs CCR1/SERPINA1,CCR5/HCST, C1QA/CD68,CCR5/S100A11 and SERPINA1/TLR1 as presenting the most significant difference in co-expression between SZ and BD. Next, a protein-protein interaction (PPI) network using the 28 differentially expressed genes as seeds revealed CASP4, TYROBP, CCR1, SERPINA1,CCR5and C1QA as having a central role in the diseases manifestation. Both co-expression and network topological analyses pointed to genes related to microglia functions. Based on this data, we suggest that differences between SZ and BP are due to genes involved with response to stimulus, defense response, immune system process and response to stress biological processes, all having a role in the communication of environmental factors to the cells and associated to microglia. |
| SCZ关键字 | schizophrenia |
| 6 | Nord J Psychiatry 2016 Feb -1: 1-6 |
| PMID | 26906930 |
| 标题 | 精神分裂症中的趋化因子基因变异。 |
| Abstract | Background Chemokines are known to play a major role in driving inflammation and immune responses in several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and Parkinson's disease. Inflammation has also been implicated in the pathogenesis ofschizophrenia. Aim We aimed to investigate a potential link between chemokines andschizophrenia并分析MCP-1-A2518G，SDF-1-3'A的作用，CCR5-delta32,CCR5-A55029G, CXCR4-C138T and CCR2-V64I gene polymorphisms in the Turkish population. Methods Genotyping was conducted by PCR-RFLP based on 140 patients and 123 unrelated healthy controls to show the relation between chemokine gene variants andschizophreniarisk. Results Frequencies ofCCR5-A55029G A genotypes andCCR5-A55029G AG genotypes were found higher in patients than the controls and even also CCR2-V64I WT:CCR5-A55029G A and CCR2-V64I 64I:CCR5-A55029G单倍型根据Bonferroni校正显着相关。但是，没有发现任何其他多态性的显着关联schizophrenia. Conclusions Our findings suggest thatCCR5-A55029G polymorphisms and CCR2-V64I WT:CCR5-A55029G A and CCR2-V64I 64I:CCR5-A55029G A haplotypes might have association withschizophrenia发病。 |
| SCZ关键字 | schizophrenia |
| 7 | J. Alzheimers Dis. 2016 Mar 52: 581-608 |
| PMID | 27031468 |
| 标题 | The Zebrafish Equivalent of Alzheimer's Disease-Associated PRESENILIN Isoform PS2V Regulates Inflammatory and Other Responses to Hypoxic Stress. |
| Abstract | PRESENILIN基因PSEN1和PSEN2的主要突变引起家族性阿尔茨海默氏病（FAD），通常在65岁之前出现发病。相比之下，PSEN1和PSEN2基因座的遗传变异似乎并没有导致疾病的零星，晚期发作形式的风险（SAD），导致怀疑这些基因在大多数AD病例中都起着作用。然而，SAD大脑中的PSEN2，PS2V的截短同工型被上调，并由缺氧和高胆固醇摄入诱导。PS2V可以增加？ - 分泌酶活性并抑制展开的蛋白质反应（UPR），但是由于缺乏合适的，遗传操纵的动物模型，因此对其功能的详细分析受到了阻碍，因为小鼠和大鼠缺乏这种preseninilin nililin同工型。我们最近表明斑马鱼具有与人PS2V相关的同工型PS1IV。使用反义的吗啡寡核苷酸，我们可以专门阻止通常在缺氧下发生的PS1IV诱导。在这里，我们利用这种能力来识别PS1IV调节的基因调节网络。当缺氧样条件下不存在PS1IV时，我们观察到控制炎症的基因表达变化（尤其是与SAD相关的IL1B和CCR5), vascular development, the UPR, protein synthesis, calcium homeostasis, catecholamine biosynthesis, TOR signaling, and cell proliferation. Our results imply an important role for PS2V in sAD as a component of a pathological mechanism that includes hypoxia/oxidative stress and support investigation of the role of PS2V in other diseases, includingschizophrenia，当这些与病理有关时。 |
| SCZ关键字 | schizophrenia |