Cell cycle checkpoint kinase 2 (CHEK2) is a checkpoint kinase that plays an important role in the DNA damage signaling network. Numerous epidemiological studies have evaluated the association between the CHEK2 I157T variant and cancer susceptibility. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CHEK2 I157T variant is associated with cancer susceptibility. PubMed, Embase (before 2012-10-1), Google Scholar, and CBMdisc were searched for studies on the relationship of the CHEK2 I157T variant and the incidence of cancer. Eligible articles were included for data extraction. The main outcome was the frequency of CHEK2 I157T polymorphisms between cases and controls. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. In total, 26,336 cases and 44,219 controls from 18 case–control studies were used in this meta-analysis, and significant associations of the CHEK2 I157T variant with cancer susceptibility were found (OR, 1.39; 95% CI, 1.19–1.63; p<0.0001), breast cancer (OR=1.58, 95% CI=1.42–1.75, p<0.00001) and colorectal cancer (OR=1.67, 95% CI=1.24–2.26, p=0.0008). We also found an association of the CHEK2 I157T variant with familial cases (OR=1.85, 95% CI=1.51–2.26, p<0.00001). However, the association was not established for other types of cancer (OR=1.09, 95% CI=0.75–1.57, p=0.66). This meta-analysis demonstrates that the CHEK2 I157T variant was an important cancer gene, which increases cancer risk, especially in breast and colorectal cancer in Caucasian, and the bioinformatic analysis showed this change was mainly attributed to the decreased hydrophobicity of CHEK2 157T.

Hypothyroidism disorders and gestational diabetes are among the most common endocrinopathies during pregnancy. We conducted a meta-analysis to investigate whether hypothyroidism in pregnancy is associated with gestational diabetes risk. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. Seven articles described the relationship between hypothyroidism and risk of gestational diabetes. This meta-analysis revealed that overt hypothyroidism was associated with an increased risk of gestational diabetes (OR 1.892, 95% CI 1.679-2.132, p < 0.001). The relative risk of gestational diabetes was also increased in subclinical hypothyroidism, with the OR of 1.558 (95% CI 1.292-1.877, p < 0.001). There was no evidence of significant association between hypothyroxinemia and risk of gestational diabetes (OR 1.394, 95% CI 0.753-2.580, p = 0.291). The OR for all of the hypothyroidism was 1.749 (95% CI 1.586-1.928, p < 0.001), and an association was found. Results of this meta-analysis indicate that hypothyroidism may be a risk factor for gestational diabetes.

Vitamin D status may influence the risk of Insulin resistance related diseases such as Type 2 diabetes (T2DM), metabolic syndrome (MetS), and polycystic ovarian syndrome (PCOS). Several studies have assessed vitamin D receptor (VDR) gene polymorphism in relationship with these diseases; however, results remain inconsistent. Our study was conducted to elucidate whether VDR Gene polymorphisms could predict insulin resistance on a large scale. A meta-analysis using MEDLINE and EMBASE, was performed up to December 16th, 2016. Studies reporting association of vitamin D gene polymorphism with incident T2DM, MetS and PCOS outcomes were included and sub-group analysis by pigment of skin and latitude were performed. A total of 28 articles based on four gene variation, and comprising 9232 participants with 5193 Insulin resistance related diseases patients were included. No significant associations of the VDR ApaI, BsmI, FokI and TaqI variant with Insulin resistance related diseases were found. However, sub-group analysis analysis showed that PCOS in TaqI (OR = 1.47, 95% CI = 1.03–2.09, P = 0.03) for T allele and MetS for G allele (OR = 1.41, 95% CI = 1.07–1.85, P = 0.01) in BsmI was significant association with VDR gene polymorphism. Simultaneously, sub-group analysis showed VDR ApaI rs7975232(G > T)variant was associated with insulin resistance related diseases in Asians (GG/GT + TT) (OR, 1.62; 95% CI, 1.03–2.53; P = 0.04) and population who lived in middle latitude district (30–60°) (GG/GT + TT) (OR, 1.22; 95% CI, 1.04–1.43; P = 0.02), VDR BsmI rs1544410 (A > G)and VDR Taq1rs731236 (T/C) variant were associated with insulin resistance related diseases in Caucasian (dark-pigmented). The results suggested that the association between insulin resistance related diseases and VDR ApaI, BsmI, FokI variant was more obvious in dark-pigmented Caucasians and Asians but not in Caucasian with white skin.

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)–induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho–mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA–mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD.