A Potential Immune-Related miRNAs Regulatory Network and Corresponding Diagnostic Efficacy in Schizophrenia.

PURPOSE: Immune-related pathways actively participate in the progression of schizophrenia (SCZ), however, roles of immune-related miRNAs in SCZ are still unclear. METHODS: A microarray expression study was conducted to explored roles of immune-related genes in SCZ. Functional enrichment analysis by using "clusterProfiler" was used to identify molecular alterations of SCZ. Protein-protein interaction (PPI) network was constructed and helped core molecular factors identification. Based on The Cancer Genome Atlas (TCGA) database, clinical significances of hub immune-related genes in cancers were also been explored. Then, correlation analyses were used to determine immune-related miRNAs. We further validated that hsa-miR-1299 could be an effective diagnostic biomarker for SCZ via analyzing multi-cohorts' data and quantitative real-time PCR (qRT-PCR). RESULTS: A total of 455 mRNAs and 70 miRNAs that were differentially expressed between SCZ and control samples. Functional enrichment analysis based on differentially expressed genes (DEGs) hinted that immune-related pathways were significantly correlated with SCZ. Furthermore, a total of 35 immune-related genes that involved in disease onset and showed significant co-expressed relationships. Hub immune-related gene CCL4 and CCL22 are valuable in tumor diagnosis and survival prediction. Furthermore, we also identified 22 immune-related miRNAs that play important roles in this disease. An immune-related miRNAs-mRNAs regulatory network was constructed to provide miRNAs regulatory roles in SCZ. Core miRNAs expression status of hsa-miR-1299 were also validated in another cohort, which suggested its diagnostic performance for SCZ. CONCLUSIONS: Our study reports the downregulation of some miRNAs in the process of SCZ are important. Shared genomics characteristics between SCZ and cancers also provide novel insights for cancers. A significant alteration of hsa-miR-1299 expression is effective as biomarker for the diagnosis of SCZ, suggesting that this miRNA could be a specific biomarker.

Effects of PM2.5 pollution and single nucleotide polymorphisms of neurotrophin signaling pathway genes acting together on schizophrenia relapse.

PURPOSE: The objective of this study was to investigate the co-effect of long-term exposure to atmospheric particulate matter PM2.5 and single nucleotide polymorphisms on schizophrenia relapse. METHODS: A total of 332 patients with schizophrenia were recruited. Genotyping of eight SNPs for five genes along the neurotrophin signaling pathway was performed by the Sequenom Massarray technology platform. Based on the data from the monitoring stations, the PM2.5 level of each patient's residence was assessed by the inverse distance weighting method using Arc GIS software. Cox regression analysis was used to determine independent risk factors. The relationship between PM2.5 levels and the risk of schizophrenia relapse was evaluated using the restricted cubic spline (RCS) method. RESULTS: In this study, a total of 191 of 332 patients with schizophrenia relapsed with hospitalization. The risk of schizophrenia relapse was 13.62 (95% CI 8.29 to 22.37) in areas with PM2.5 concentrations of 48.43 to 75.35 µg/m3. The risk of schizophrenia relapse was 5.81 (95% CI 3.58-9.42, p < 0.001) and 13.62 (95% CI 8.29-22.37, p < 0.001) in the exposure categories Q3 and Q4, respectively, compared with Q1, and non-linear relationship between cumulative PM2.5 exposure and risk of schizophrenia relapse. A greater association was observed in the YWHAB gene polymorphic locus rs6031849 genotype TG (Hazard ratio 16.62, 95% CI 5.73 to 48.24). CONCLUSIONS: PM2.5 levels, YWHAB gene polymorphism locus rs6031849, and gender jointly influenced schizophrenia relapse, with long-term exposure to high levels of PM2.5 having the greatest effect on schizophrenia relapse.

CALM1 rs3179089 polymorphism might contribute to coronary artery disease susceptibility in Chinese male: a case-control study.

BACKGROUND: Calmodulin 1 (CALM1) mutations are involved in the development of coronary artery disease (CAD). However, the relationship of CALM1 rs3179089 polymorphism with CAD is unknown. OBJECTIVE: This study aimed to identify the relationship of CALM1 rs3179089 polymorphism with CAD susceptibility, CALM1 expression, blood pressure, blood glucose, blood coagulation and serum lipid levels of CAD patients. METHODS: 550 CAD patients and 550 control subjects were genotyped for CALM1 using Sequenom MassARRAY technology. CALM1 expression level was measured by quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: CALM1 mRNA expression was higher in CAD patients than that in control subjects (P < 0.001). CAD patients with CC genotype had higher CALM1 mRNA expression level than control subjects with CC genotype (P = 0.006). Genotypic frequency of rs3179089 was different between male patients of CAD and control subjects (P = 0.045). Rs3179089 polymorphism was related to CAD risk of males in recessive model (P = 0.039). Moreover, rs3179089 polymorphism was associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), and D-Dimer (D-D) level of patients with CAD in recessive model (P = 0.013 for SBP; P = 0.034 for DBP; P = 0.004 for FPG; P = 0.046 for D-D). In addition, rs3179089 polymorphism was correlated with low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) serum levels of patients with CAD in both addictive (P = 0.025 for LDL-C; P = 0.001 for TC) and recessive models (P = 0.001 for LDL-C; P = 0.001 for TC). CONCLUSION: CALM1 expression is associated with development of CAD. CALM1 rs3179089 polymorphism affects CAD susceptibility in males, and blood pressure, blood glucose, blood coagulation and serum lipid of CAD patients.

Association of CALM1 rs3179089 Polymorphism with Ischemic Stroke in Chinese Han Population.

A quantitative transcriptomics analysis has reported that Calmodulin 1 (CALM1) is highly expressed in human brain tissues. This study aims to evaluate the relationship between CALM1 rs3179089 polymorphism and ischemic stroke (IS) in Chinese Han population. A total of 550 patients with IS and 550 control subjects were recruited and genotyped using Sequenom MassArray technology. The mRNA expression of CALM1 was measured using quantitative real-time polymerase chain reaction. CALM1 mRNA expression was significantly higher in patients with IS than that in control subjects (P = 0.006). The genomic frequency distribution was significantly different between female patients with IS and female controls (χ2 = 6.043, P = 0.047). In recessive model, CALM1 rs3179089 polymorphism was associated with the risk of IS in female patients. GG genotype significantly increased the risk of IS compared with the CC+GC genotype in females (OR 8.68, P = 0.042; adjusted OR 8.72, Padj = 0.042). Rs3179089 polymorphism was associated positively with plasmas D-Dimer of patients with IS in recessive model (ßa = 3.24, P = 0.018; ßb = 3.20, Padj = 0.019). Moreover, rs3179089 polymorphism was related positively to thrombin time of patients with IS in addictive (ßa = 2.32, P = 0.005, ßb = 2.26, Padj=0.006) and recessive model (ßa = 11.19, P = 0.001, ßb = 11.13, Padj = 0.001). CALM1 expression was involved in the development of IS. CALM1 rs3179089 polymorphism was associated with IS risk in Chinese females, and related to blood coagulation of IS patients.