No abstract

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in pathogenesis of asthma. A high level of MIF has been detected in bronchoalveolar lavage fluid, serum and sputum in asthma. Polymorphisms associated with inflammatory diseases exist in the promoter region of MIF, which alter its expression. The aim of this study was to evaluate the potential relationship between functional polymorphisms of MIF and childhood asthma in a northeastern Chinese population. The study consisted of a set of 41 trios and an independent sample set of 189 childhood asthma patients and 261 healthy controls. We genotyped MIF-173G/C using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Additionally, MIF-794CATT(5-8) microsatellite polymorphism was genotyped by polyacrylamide gel electrophoresis (PAGE). A statistically significant difference in the distribution of the MIF-173C allele between patients and controls [P = 0.01, odds ratio (OR) = 1.55, 95% confidence interval (CI) = 1.13-2.18] was observed. In addition, the frequency of the MIF-173CC genotype was higher in asthmatic children (P < 0.01, OR = 3.37, 95% CI = 1.27-8.93). No difference in the distribution of CATT(5-8) was found between patients and healthy controls. Haplotype analysis showed that only the MIFCATT(7)-173C haplotype was associated with greater susceptibility to childhood asthma (P = 0.03, OR = 1.54, 95% CI 1.03-2.28). However, the transmission disequilibrium test confirmed a positive association between MIF-173G/C and childhood asthma (P = 0.005), and the absence of an association between the MIF-794CATT(5-8) and the disease. These preliminary results suggest an association between the MIF-173C allele and childhood asthma.

Background: Aberrant DNA methylation, especially tumor suppressor gene hypermethylation, is a well-recognized biomarker of initial tumorogenesis stages. FAT4 and SOX11 are putative tumor suppressor genes and can be down-regulated by hypermethylation in various cancers tissues. However, in peripheral blood leukocytes, the association between these two genes methylation status, as well as the effects of gene-environment interactions, and gastric cancer (GC) risk remain unclear.Methods: A hospital-based case-control study including 375 cases and 394 controls was conducted. Peripheral blood leukocytes DNA methylation status were detected by methylation-sensitive high-resolution melting (MS-HRM) assay. Logistic regression was adopted to analyze the relationship of FAT4 and SOX11 methylation with GC susceptibility.Results: Positive methylation (Pm) and total positive methylation (Tpm) of FAT4 were significantly increased the risk of GC (OR = 2.204, 95% CI: 1.168-4.159, P = 0.015; OR = 1.583, 95% CI: 1.031-2.430, P = 0.036, respectively). Compared with controls, cases exhibited higher SOX11 Pm frequencies with OR of 2.530 (95% CI: 1.289-4.969, P = 0.007). Nonetheless, no statistically significant association between SOX11 Tpm and GC risk was observed. Additionally, interactions between FAT4 Tpm and increased consumption of freshwater fish (≥1 times/week) displayed an antagonistic effect on GC (OR = 0.328, 95% CI: 0.142-0.762, P = 0.009), and high salt intake interacted with SOX11 Tpm also showed statistically significant (OR = 0.490, 95% CI: 0.242-0.995, P = 0.048).Conclusions: FAT4 aberrant methylation in peripheral blood leukocytes and gene-environment interactions were associated with the risk of GC, while SOX11 was controversial and needed to be more investigated.

Wnt signaling pathway activation plays a critical role in biological processes of tumor progression. SOX9 belongs to the sry-related high-mobility group box (SOX) family and is a key transcription factor in the development and differentiation of multiple cell lineages. The purpose of this study was to investigate whether suppression of Wnt signaling pathway by PPARγ gene affects target SOX9 gene expression. The pEGFP-N1-PPARγ overexpression recombinant plasmid was structured by molecular biology technology. The overexpression plasmid and empty vector pEGFP-N1 were transfected into three types of human gastric cancer cell lines, with different levels of differentiation, MKN-28, SGC-7901 and BGC-823. The PPARγ, β-catenin and SOX9 mRNA levels and proteins were examined by real-time PCR and Western blot analysis. The pEGFP-N1-PPARγ recombinant plasmid was constructed and transfected into MKN-28, SGC-7901 and BGC-823 successfully. High expression of PPARγ (p < 0.05) for transfection recombinant plasmid group induced obviously decreased expression of β-catenin (p < 0.05), whereas SOX9 expression decreased significantly (p < 0.05) compared with the transfection empty vector group and normal comparison group. PPARγ can suppress β-catenin expression in Wnt signaling pathway and its downstream effector SOX9 expression in gastric cancer cells.

The aim of this study was to explore the association between polymorphisms in signal transducer and activator of transcription protein 3 (STAT3) and the risk of gastric cancer. In the present study, a case-control study was conducted in which rs2293152 and rs744166 polymorphisms in STAT3 were analyzed in 209 Chinese patients with gastric cancer and 294 cancer-free controls. The genotypes were determined by polymerase chain reaction restriction fragment length polymorphism method. For the rs744166 polymorphism, the TC genotype (adjusted OR = 0.60, 95% CI = 0.39–0.92, and P = 0.020) and CC genotype (adjusted OR = 0.41, 95% CI = 0.21–0.80, and P = 0.009) were associated with a decreased risk of gastric cancer compared to the TT genotype. However, rs2293152 did not show any difference in gastric cancer risk between patients and controls in the CG/CC genotype compared to the GG genotype. Besides, the SNP effects were additive to the effects of environmental factors without any interaction between them in the susceptibility to gastric cancer. Collectively, rs744166 polymorphism might be significantly associated with a decreased risk of gastric cancer in a Chinese population. Additionally, polymorphisms in STAT3, along with environmental factors, might be associated with the development of gastric cancer.