Abstract
BackgroundGlucokinase (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.MethodsDatabases 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.ResultsA 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.ConclusionsThis 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.
Highlights
Type 2 diabetes (T2D) is a complex metabolic disease characterised by hyperglycemia, insulin resistance, impaired insulin secretion due to pancreatic b-cell defects and increased hepatic glucose production
This meta-analysis demonstrated that the 230G.A polymorphism of GCK is a risk factor associated with increased type 2 diabetes (T2D) susceptibility, but these associations vary in different ethnic populations
Search term combinations were keywords relating to the glucokinase gene (e.g., ‘‘glucokinase’’, ‘‘GCK’’, and ‘‘MODY 2’’) in combination with words related to T2D (e.g., ‘‘type 2 diabetes mellitus’’, ‘‘T2DM’’, ‘‘type 2 diabetes’’, ‘‘T2D’’, ‘‘non-insulin-dependent diabetes mellitus’’ and ‘‘NIDDM’’) and polymorphism or variation
Summary
Type 2 diabetes (T2D) is a complex metabolic disease characterised by hyperglycemia, insulin resistance, impaired insulin secretion due to pancreatic b-cell defects and increased hepatic glucose production. The genetic contribution to T2D is well recognized, the current set of 56 established susceptibility loci, identified primarily through largescale genome-wide association studies (GWAS), captures at best 10% of familial aggregation of the disease [1,2,3]. This has maintained interest in other biochemical and genetic factors that might contribute to the underlying pathophysiology of the disease. 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. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis
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