Genetic polymorphisms in the ESR1 gene and cerebral infarction risk: a meta-analysis.

A number of studies have documented that estrogen receptor α (ESR1) may play an important role in the development and progression of cerebral infarction, but many existing studies have yielded inconclusive results. This meta-analysis was performed to evaluate the relationships between ESR1 genetic polymorphisms and cerebral infarction risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013, without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Seven case-control studies were included with a total of 1471 patients with cerebral infarction and 4688 healthy control subjects. Two common single-nucleotide polymorphisms (SNPs) in the ESR1 gene (rs2234693 T>C and rs9340799 A>G) were assessed. Our meta-analysis results revealed that ESR1 genetic polymorphisms might increase the risk of cerebral infarction. Subgroup analysis by SNP type indicated that both rs2234693 and rs9340799 polymorphisms in the ESR1 gene were strongly associated with an increased risk of cerebral infarction. Further subgroup analysis by ethnicity showed significant associations between ESR1 genetic polymorphisms and increased risk of cerebral infarction among both Asians and Caucasians. In the stratified subgroup analysis by gender, the results suggested that ESR1 genetic polymorphisms were associated with an increased risk of cerebral infarction in the female population. However, there were no statistically significant associations between ESR1 genetic polymorphisms and cerebral infarction risk in the male population. Meta-regression analyses also confirmed that gender might be a main source of heterogeneity. Our findings indicate that ESR1 genetic polymorphisms may contribute to the development of cerebral infarction, especially in the female population.

Correlations of MCP-1 -2518A>G polymorphism and serum levels with cerebral infarction risk: a meta-analysis.

This meta-analysis was performed to evaluate the relationships between the monocyte chemoattractant protein-1 (MCP-1) -2518A>G (rs1024611 A>G) polymorphism and its serum levels, and the risk of cerebral infarction. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1st, 2013 without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) or standardized mean difference (SMD) with their 95% confidence intervals (95% CIs) were calculated. Twelve case-control studies that met all the inclusion criteria were included in this meta-analysis. A total of 1272 patients with cerebral infarction and 1210 healthy control subjects were involved in this meta-analysis. Our meta-analysis results reveal that the MCP-1 -2518A>G polymorphism might increase the risk of cerebral infarction (A allele vs. G allele: OR=1.37, 95% CI: 1.18-1.60, p<0.001; GA+AA vs. GG: OR=1.33, 95% CI: 1.09-1.62, p=0.005; respectively). Furthermore, cerebral infarction patients had higher levels of serum MCP-1 than did healthy control subjects (SMD=2.96, 95% CI: 2.00-3.92, p<0.001). Statistical analysis revealed no evidence of publication bias in this meta-analysis (all p>0.05). Our findings indicate that the MCP-1 -2518A>G polymorphism and serum MCP-1 levels may contribute to the development of cerebral infarction. Thus, the MCP-1 -2518A>G polymorphism and serum MCP-1 levels could be potential biomarkers for the early detection of cerebral infarction.

Metformin inhibits glioma cell U251 invasion by downregulation of fibulin-3.

Fibulin-3 has been considered as a regulator of glioma cell invasion, but little is known about the molecules regulating fibulin-3 expression. Metformin, an oral antidiabetic drug in the biguanide class, is known to inhibit proliferation and metastasis in a variety of cancer cells. In the present study, we determined the effect of metformin on the expression of fibulin-3 in U251 Human glioma cells. Metformin potently suppressed U251 cell adhesion and invasion. Metformin inhibited the expression of fibulin-3 at the transcriptional level. Moreover, metformin abolished the protein expression of fibulin-3 in a concentration-dependent manner. Furthermore, this compound suppressed the expression of matrix metalloproteinase-2, a key effector of glioma cell invasion, regulated by fibulin-3. Taken together, our results suggest that metformin abolishes fibulin-3 expression and subsequently inhibits invasion of glioma cells.