Associations of KCNQ1 Polymorphisms with the Risk of Type 2 Diabetes Mellitus: An Updated Meta-Analysis with Trial Sequential Analysis.

BACKGROUND: Previous studies have examined the role of the KQT-like subfamily Q member1 (KCNQ1) gene polymorphisms on the risk of type 2 diabetes mellitus (T2DM), but the findings are inconclusive. OBJECTIVE: To examine the association between the KCNQ1 gene polymorphisms and the risk of T2DM using an updated meta-analysis with an almost tripled number of studies. METHODS: Five electronic databases, such as PubMed and Embase, were searched thoroughly for relevant studies on the associations between seven most studied KCNQ1 gene polymorphisms, including rs2237892, rs2237897, rs2237895, rs2283228, rs231362, rs151290, and rs2074196, and T2DM risk up to September 14, 2019. The summary odds ratios (ORs) with their 95% confidence intervals (CIs) were applied to assess the strength of associations in the random-effects models. We used the trial sequential analysis (TSA) to measure the robustness of the evidence. RESULTS: 49 publications including 55 case-control studies (68,378 cases and 66,673 controls) were finally enrolled. In overall analyses, generally, increased T2DM risk was detected for rs2237892, rs2237895, rs2283228, rs151290, and rs2074196, but not for rs231362 under all genetic models. The ORs and 95% CIs for allelic comparison were 1.23 (1.14-1.33) for rs2237892, 1.21 (1.16-1.27) for rs2237895, 1.27 (1.11-1.46) for rs2237897, 1.25 (1.09-1.42) for rs2283228, 1.14 (1.03-1.27) for rs151290, 1.31 (1.23-1.39) for rs2074196, and 1.16 (0.83, 1.61) for rs231362. Stratified analyses showed that associations for rs2237892, rs2237895, rs2283228, and rs151290 were more evident among Asians than Caucasians. TSA demonstrated that the evidence was sufficient for all polymorphisms in this study. The genotypes of the three SNPs (rs2237892, rs2283228, and rs231362) were significantly correlated with altered KCNQ1 gene expression. CONCLUSION: This meta-analysis suggested that KCNQ1 gene polymorphisms (rs2237892, rs2283228, rs2237895, rs151290, and rs2074196) might be the susceptible factors for T2DM, especially among Asian population.

Effects of dairy products, calcium and vitamin D on ovarian cancer risk: a meta-analysis of twenty-nine epidemiological studies.

Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case-control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.