The results clearly showed that the inhibition effect of rs57137919A on ABCG1 promoter activity was more potent under LXR agonist stimulation in different cell lines, suggesting that the activation of the ABCG1 gene promoter driven by LXR agonist might be suppressed by the rs57137919A allele. It is widely accepted that oxysterols, as the ligands for LXR activation, can activate the ABCG1 promoter and upregulate ABCG1 transcription in LXR-dependent mechanisms. Based on our findings, it is reasonable to speculate that the rs57137919A allele can also exert its inhibition effect on LXR-dependent ABCG1 expression activated by the ox-LDL loading of macrophages. In our previous study using the PATCHTM public 1.0 prediction software, we predicted that putative regulatory elements, VDR and GAGA factor, may bind to site rs57137919 in the ABCG1 promoter region. In the present study, EMSA clearly showed that the wild-type G site probes, rather than mutant A site probes, were capable of specifically binding the protein extracted from PBMC-derived macrophages or THP-1 cell nuclei, suggesting that the rs57137919G.A variant would weaken the binding between the ABCG1 promoter and the transcription factor, and consequently reduce ABCG1 promoter transcription. Based on these results, it is plausible that the differences in ABCG1 gene expression may have resulted, at least partly, from the modulatory effect of the various rs57137919 sequences on DNA-protein interactions in the promoter region. However, PCS1055 dihydrochloride whether the phenotypic outcomes are relevant to DNAprotein interactions is yet to be verified. Therefore, it will be beneficial to conduct additional studies to substantiate the regulatory factors and mechanisms that might be involved. Previous in vitro studies have suggested that ABCG1 is responsible for sterol efflux from cholesterol-loaded macrophage foam cells to mature HDL. Further, Wang et al. reported that macrophages lacking ABCG1 expression impaired cholesterol efflux to HDL and significantly reduced reverse cholesterol transport in vivo. Studies in cell lines showed that ABCG1, rather than ABCA1, can specifically mediate 7- ketocholesterol and 7b-hydroxycholesterol efflux from cells to HDL. These are two oxysterols existed in oxidized LDL with the oxidation at C7-position. Within human atherosclerotic lesions, 7-ketocholesterol and 7b-hydroxycholesterol exerted cytotoxic effects in promoting macrophage apoptosis ; similar findings were reported in studies using ABCG12/2 mice. Herein, we found that the ABCG1 promoter rs57137919A was associated with a significantly downregulated ABCG1 expression and attenuated cholesterol efflux, which may have led to the accumulation of specific oxysterols in macrophages and accelerated cell apoptosis. Macrophage apoptosis plays a critical role in the development of atherosclerosis. In fatty streak lesions, which form the early stage of atherosclerosis, an increase in macrophage apoptosis is atheroprotective, while in advanced atherosclerotic lesions, an increase in macrophage apoptosis leads to necrotic core development, contributing to vulnerable plaque formation and thrombosis. Gastric cancer is one of the most frequently occurring malignancies and keeps a major cause of cancer mortality all over the world. In China, there are about 360,000 individuals die of gastric cancer every year. Though the incidence has decreased in recent years in the West, the survival is still worse. Over the past decades, great effort has been exerted to elucidate the pathogenesis of gastric cancer. However, the complex mechanism of gastric carcinogenesis is still uncovered. Accumulating evidence indicate that long-term chronic inflammation is one of the leading causes of tumorigenesis. Release of pro-inflammatory mediators and increased local levels of oxygen and nitrogen species can contribute to carcinogenesis. The dysregulated production of cytokines in inflammatory microenvironment stimulates the expression of genes associated with cancer development and modifies structural features of microenvironment to accelerate cancer initiation and progression. Tumor microenvironment consists of various stromal cells, including infiltrating immune cells, carcinoma-associated fibroblasts, mesenchymal stem cells, and blood and lymphatic vascular networks. These cells interact with each other and constitute inflammatory microenvironment and contribute to tumorigenesis. Among the stromal cells, macrophages, as important immune regulatory cells, play a dominant role in managing inflammation in tumor microenvironment. For example, macrophages isolated from tumor microenvironment of breast cancer patients secret chemotactic cytokines to augment metastasis of carcinoma cells. Macrophages have also been shown to promote inflammatory response and tumorigenesis through impacting on expression of inflammatory cytokines and altering the molecular oncogenic programs within epithelial cells. Mesenchymal stem cells are another major component of the tumor microenvironment and are considered as the precursor cells of cancer associated mesenchymal cells and endothelial cells. The previous studies have indicated that MSCs secret soluble factors to promote cancer cell proliferation and metastasis. In an inflammation-associated gastric cancer model, MSCs could be activated towards CAFs to increase chronic inflammation and cancer progression. Furthermore, MSCs have been reported to recruit monocytes/macrophages to promote tumor growth in a CCR2-depedent manner. Interactions between macrophages and MSCs produce an activated, pro-inflammatory phenotype with high CXCL10 and IL-6 secretion, which may influence the inflammatory microenvironment. Gastric cancer is a classic model of chronic inflammation to cancer.