There are inconsistent data on the association of risk of hepatitis virus infection and hepatitis virus-related diseases with the toll-like receptor 3 (TLR3) gene.Several common polymorphism sites were targeted to assess the risk of HBV infection, HCV infection, and HBV-related diseases.Meta-analysis combining data for 3547 cases and 2797 controls from 8 studies was performed in this study. Pooled ORs were calculated to measure the risk of hepatitis virus infection and hepatitis virus-related diseases. Fixed-effects pooled ORs were calculated using the Mantel-Haenszel method.The TLR3 gene was associated with a significantly increased risk of HBV-related diseases among 1355 patients and 1130 controls ([pooled OR, [95%CI]: 1.30, [1.15–1.48] for dominant; 1.77, [1.35–2.31] for recessive; 1.28 [1.16–1.41] for allele frequency). Subgroup analyses by a polymorphism site indicated an increased risk of HCV infection in relation to the TT/CT genotypes of rs3775291 (1.50 [1.11–2.01]), and a decreased risk ascribed to the T allele (0.20 [0.16–0.25]). We also noted an association between rs3775291 and significantly increased risk of HBV-related diseases (2.23 [1.55–3.21]). No significant inter-study heterogeneity or publication bias was detected in the analyses.These data suggest a likely effect on the risk to infect HCV and develop HBV-related diseases for the TLR3 gene. Large-scale studies with racially diverse populations are required to validate these findings.
Acute coronary syndrome (ACS) is characterized by atherosclerotic plaque rupture with a high incidence of recurrent ischemic events. Several microRNAs are found to be aberrantly expressed in atherosclerotic plaques. This study aims to investigate the effects of microRNA‐9 (miR‐9) on vulnerable atherosclerotic plaque and vascular remodeling in ACS and underlying mechanisms. Microarray‐based gene expression profiling was used to identify differentially expressed genes related to ACS and regulatory miRNAs. Oxidized low‐density lipoprotein (lectin‐like) receptor 1 (OLR1) was identified to be aberrantly activated in ACS and regulated by miR‐9. OLR1 was verified as a target gene of miR‐9 by bioinformatics prediction and dual luciferase reporter gene assay. The atherosclerotic models were induced in ApoE−/− mice, in which the agomir or antagomir of miR‐9, or small interfering RNA (siRNA) against OLR1 were separately introduced. Serum lipid levels and expression of vascular remodeling and inflammatory response‐related factors were determined, respectively. On the basis of the obtained results, in the atherosclerosis mice treated with the agomir of miR‐9 and siRNA against OLR1, the p38‐mitogen‐activated protein kinase (p38MAPK) pathway was inhibited; levels of triglyceride, total cholesterol, low‐density lipoprotein cholesterol, tumor necrosis factor‐α, interleukin‐6, and vascular endothelial growth factor were reduced, but the high‐density lipoprotein cholesterol level was increased, along with decreased vulnerable atherosclerotic plaque area and enhanced vascular remodeling. Taken together, these findings suggested an inhibitory role miR‐9 acts in the formation of vulnerable atherosclerotic plaques in ACS mice, along with a promoted vascular remodeling, via a negative feedback regulation of OLR1‐mediated p38MAPK pathway.
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