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

• Published in: PloS one Vol. 8; no. 2; p. e55727
• Main Authors: Fu, Da, Cong, Xianling, Ma, Yushui, Cai, Haidong, Cai, Mingxiang, Li, Dan, Lv, Mingli, Yuan, Xueyu, Huang, Yinghui, Lv, Zhongwei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.02.2013; Public Library of Science (PLoS)
• Subjects: Asians - genetics; Biology; Blood Glucose; Confidence intervals; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Fasting; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease; Glucokinase; Glucokinase - genetics; Glucokinase - metabolism; Glucose; Glucose - metabolism; Glycolysis; Health risks; Humans; Hypothesis testing; Insulin; Insulin resistance; Insulin secretion; Isoenzymes; Medicine; Meta-analysis; Minority & ethnic groups; Mutation; Nuclear medicine; Phosphorylation; Polymorphism; Polymorphism, Genetic; Population; Publication Bias; Risk; Risk factors; Secretion; Studies; Type 2 diabetes; Whites - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055727

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. 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. 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. 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.