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Fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes associated with obesity have been identified through Genome-wide Association Studies. However, no multiple loci interaction studies have been conducted in the Chinese population. This study investigated whether the combined effects of FTO and MC4R increase the risk of obesity in children and adolescents living in Northwest China.A total of 370 subjects (170 overweight/obese and 200 normal BMI subjects according to the Working Group on Obesity in China criteria) were enrolled using the random sampling method. FTO rs9939609 and rs9935401 and MC4R rs12970134 and rs17782313 interactions were analysed through generalized multifactor dimensionality reduction, and logistic regression models were used to calculate the risk of the relationship between genotypes and obesity.Generalized multifactor dimensionality reduction analysis showed a significant gene-gene interaction among FTO rs9939609/MC4R rs12970134/MC4R rs17782313, with a score of 10/10 for the cross-validation consistency and 9 for the sign test (p=0.011). A 2.453-fold increased risk of obesity was observed in individuals carrying the genotypes of FTO rs9939609 TA/AA, MC4R rs12970134 GA/AA, and MC4R rs17782313 TC/CC (adjusted for age, sex, and ethnicity; 95% CI=1.12-5.37, p=0.025).Our results suggested that FTO rs9939609, MC4R rs12970134, and MC4R rs17782313 are strongly associated with obesity. The combined effects were highly significant on obesity in children and adolescents living in Northwest China.

MC4R (melanocortin-4 receptor) gene polymorphisms have been associated with serum triglycerides (TG) in Caucasians and Japanese, but no reports are available Chinese. The purpose of this study was to find whether there was an association of rs17782313 polymorphisms at the MC4R gene with serum TG in elderly Chinese.2,012 over 40 years participated in a cross-sectional study in which their body mass index (BMI), TG, high density lipoprotein-cholesterol (HDL-C), and MC4R rs17782313 polymorphisms were determined.For women, carriers of the T/T genotype had significantly lower serum TG than those with C/C genotype (p=0.006). Carriers of the C/C genotype of this polymorphisms exhibited significantly lower fasting HDL-C levels compared with T/T and T/C genotypes (p=0.025), and increased glycosylated hemoglobin (HbA1c) (p=0.043), but no change in blood pressure. Higher serum TG in carriers of the C/C genotype of MC4R gene remained stable after adjustment for age, smoking, drinking, BMI, waist circumference (WC) and three or more components of the metabolic syndrome (MS) by multivariable linear regression (p=0.01) in women. The carriers of the C/C genotype of MC4R gene showed significantly greater odds ratio for TG than T/C and T/T genotypes, even when adjusted for age, smoking, drinking, BMI and WC in women.The rs17782313 C/C genotype is associated with higher TG levels in older Chinese women.背景与目的：研究显示高加索人和日本人的黑色素皮质激素-4受体（MC4R） 基因多态性与血清甘油三酯（TG）相关，但没有关于中国人的报道。本研究 的目的是研究黑色素皮质激素-4受体基因rs17782313多态性是否与中国老年人 血清甘油三酯有关。方法与研究设计：本研究采用横断面的研究方法调查了 2012位年龄在40岁以上的成年人，测定其体质指数、甘油三酯、高密度脂蛋白 胆固醇以及黑色素皮质激素-4受体基因rs17782313多态性等指标。结果：携带 T/T基因型的女性血清甘油三酯明显低于携带C/C基因型的女性（p=0.006）。 携带C/C基因型的女性的高密度脂蛋白胆固醇则明显低于携带T/T和T/C基因型 的女性（p=0.025），但其糖化血红蛋白显著高于携带T/T和T/C基因型的女性 （p=0.043），血压无统计学意义。在校正了年龄、吸烟、饮酒、体质指数、 腰围和代谢综合征等因素后，多元线性回归分析发现携带C/C基因型的女性有 较高的血清甘油三酯（p=0.01）。在女性中，即使校正了年龄、吸烟、饮酒、 体质指数和腰围，携带C/C基因型的女性甘油三酯的比值比（OR值）仍然显 著高于携带T/C和T/T基因型的女性。结论：中国老年女性的黑色素皮质激素-4 受体基因rs17782313的C/C基因型与较高的血清甘油三酯有关。.

Non-small cell lung cancer (NSCLC) is highly prevalent and needs novel therapies. Melanoma-associated antigen 3 (MAGE-A3) is a lung cancer antigen and calreticulin (CALR) can modulate immune responses. Our previous study has shown that up-regulated MAGE-A3 and CALR expression inhibits the proliferation and invasion of glioma cells. In this study, we examined the effect of adenovirus (Ad)-mediated MAGE-A3 and/or CALR expression on the proliferation, invasion, and apoptosis of human NSCLC cells and on the vascular tube formation of human endothelial cells as well as on dendritic cell (DC) activation and induced CD8(+) cytotoxic T lymphocyte (CTL) activity in vitro. We found that low levels of CALR and MAGE-A3 were expressed by A549 cells, but only very low CALR was expressed by DC. Up-regulated CALR and MAGE-A3 expression by infection with Ad-CALR/MAGE-A3 significantly inhibited the proliferation and invasion, but promoted the apoptosis of A549 cells. Up-regulated CALR and MAGE-A3 expression significantly inhibited cyclin D1 expression and the AKT, ERK1/2 and NF-κB expression and phosphorylation in A549 cells. Up-regulated CALR expression inhibited the tube formation in human endothelial cells. Up-regulated CALR and MAGE-A3 expression synergistically enhanced classical DC activation by enhancing IL-12, but reducing IL-10 secretion. Furthermore, CTLs induced by up-regulated CALR and MAGE-A3 expressing DCs synergistically triggered A549 cell apoptosis, which was abrogated by treatment with anti-HLA I, but not anti-HLA II antibodies. Moreover, CTLs induced by CALR and MAGE-A3-expressing DCs had a higher frequency of A549-specific IFN-γ-secreting T cells. Our data indicated that up-regulated CALR and MAGE-A3 expression inhibited the carcinogenesis of NSCLC by modulating the AKT, ERK MAPK and NF-κB signaling and enhanced classical DC activation and MAGE-A3-specific CTL cytotoxicity. Therefore, our findings may provide new insights in understanding the role of CALR in modulating antigen-specific T cell immunity and may aid in the design of new therapies for NSCLC.

To investigate the relationship of ionized calcium and 25-(OH) D level in serum with obesity in order to provide theoretical basis for preventing obesity-related diseases.Base on a cross-sectional study, 169 overweight/obese subjects (92 men: age (37.76 +/- 17.56) years, 77 women: age (38.79 +/- 17.40) years) and 169 normal weight control subjects (92 men: age (36.24 +/- 17.28) years, 77 women: age (32.32 +/- 13.07) years) were selected in a 1:1 case-control matches. 25-(OH) D was assessed by ELISA. Serum ionized calcium was measured by flame atomic absorption spectrophotometry. The relationship of ionized calcium and 25-(OH) D level in serum with obesity was analyzed by using a Logistic regression model.The average serum ionized calcium in overweight or obese subjects was(46.9 +/- 20.7) mg/L and that in normal control subjects was (63.2 +/- 19.5) mg/L (P0.001). Serum 25-(OH) D of overweight or obese was lower than normal control subjects ((48.3 +/- 16.7) nmmol/L vs. (63.8 +/- 35.4) nmmol/L, P0.001). Serum ionized calcium and 25-(OH) D was independently associated with body mass index in a logistic regression model [OR = 0.959, 95% CI 0.945-0.973; OR = 0.435, 95% CI 0.329-0.575].Serum 25-(OH) D levels in obesity group was lower than that in control group. The results suggest that vitamin D might play an important role in the risk of developing obesity.