Background: Glucokinase (GCK) 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 GCK 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. Methods: 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. Results: 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; P<10-4) was found for the GCK -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, P = 0.001) compared with G/G genotype. Conclusions: This meta-analysis demonstrated that the -30G>A polymorphism of GCK is a risk factor associated with increased T2D susceptibility, but these associations vary in different ethnic populations. © 2013 Fu et al.
Fu, D., Cong, X., Ma, Y., Cai, H., Cai, M., Li, D., … Lv, Z. (2013). Genetic Polymorphism of Glucokinase on the Risk of Type 2 Diabetes and Impaired Glucose Regulation: Evidence Based on 298, 468 Subjects. PLoS ONE, 8(2). https://doi.org/10.1371/journal.pone.0055727