Genetic Polymorphism of Glucokinase on the Risk of Type 2 Diabetes and Impaired Glucose Regulation: Evidence Based on 298, 468 Subjects

<div><p>Background</p><p>Glucokinase (<i>GCK</i>) is the key glucose phosphorylation enzyme which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) based on its enzyme function as the first rate-limiting step in the glycolysis pathway and regulates glucose-stimulated insulin secretion. In the past decade, the relationship between <i>GCK</i> and T2D has been reported in various ethnic groups. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis.</p> <p>Methods</p><p>Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.</p> <p>Results</p><p>A total of 24 articles involving 88, 229 cases and 210, 239 controls were included. An overall random-effects per-allele OR of 1.06 (95% CI: 1.03–1.09; <i>P</i><10⁻⁴) was found for the <i>GCK</i> −30G>A polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians; whereas no significant associations were found among Asians. In addition, we found that the −30G>A polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. Besides, −30G>A homozygous was found to be significantly associated with increased fasting plasma glucose level with weighted mean difference (WMD) of 0.15 (95%: 0.05–0.24, <i>P</i> = 0.001) compared with G/G genotype.</p> <p>Conclusions</p><p>This meta-analysis demonstrated that the −30G>A polymorphism of <i>GCK</i> is a risk factor associated with increased T2D susceptibility, but these associations vary in different ethnic populations.</p> </div

Meta-analysis of the <i>GCK</i> −30G>A polymorphism on type 2 diabetes risk.

a<p>Cochran’s chi-square Q statistic test used to assess the heterogeneity in subgroups.</p>b<p>Cochran’s chi-square Q statistic test used to assess the heterogeneity between subgroups.</p

Meta-analysis of weighted mean differences (WMD) of fasting plasma glucose levels between GG and GA genotype of −30G>A polymorphism.

<p>Meta-analysis of weighted mean differences (WMD) of fasting plasma glucose levels between GG and GA genotype of −30G>A polymorphism.</p

Forest plot for the overall association between the <i>GCK</i>−30G>A polymorphism and impaired glucose regulation risk.

<p>Forest plot for the overall association between the <i>GCK</i>−30G>A polymorphism and impaired glucose regulation risk.</p

Forest plot for the overall association between the <i>GCK</i>−30G>A polymorphism and type 2 diabetes risk.

<p>Forest plot for the overall association between the <i>GCK</i>−30G>A polymorphism and type 2 diabetes risk.</p

Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA/microRNA Delivery

Antiosteoporosis gene-based drug development strategies are presently focused on targeting osteoblasts to either suppress bone loss or increase bone mass. Although siRNA/microRNA-based gene therapy has enormous potential, it is severely limited by the lack of specific cell-targeting delivery systems. We report an osteoblast-targeting peptide (SDSSD) that selectively binds to osteoblasts <i>via</i> periostin. We developed SDSSD-modified polyurethane (PU) nanomicelles encapsulating siRNA/microRNA that delivers drugs to osteoblasts; the data showed that SDSSD–PU could selectively target not only bone-formation surfaces but also osteoblasts without overt toxicity or eliciting an immune response <i>in vivo</i>. We used the SDSSD–PU delivery system to deliver anti-miR-214 to osteoblasts and our results showed increased bone formation, improved bone microarchitecture, and increased bone mass in an ovariectomized osteoporosis mouse model. SDSSD–PU may be a useful osteoblast-targeting small nucleic acid delivery system that could be used as an anabolic strategy to treat osteoblast-induced bone diseases