title: Genetic polymorphism of glucokinase on the risk of type 2 diabetes and impaired glucose regulation: evidence based on 298,468 subjects.
abstract: 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.
authors: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors: Da
authors: D
authors: Fu
authors: Xianling
authors: X
authors: Cong
authors: Yushui
authors: Y
authors: Ma
authors: Haidong
authors: H
authors: Cai
authors: Mingxiang
authors: M
authors: Cai
authors: Dan
authors: D
authors: Li
authors: Mingli
authors: M
authors: Lv
authors: Xueyu
authors: X
authors: Yuan
authors: Yinghui
authors: Y
authors: Huang
authors: Zhongwei
authors: Z
authors: Lv
mesh_terms: D044466:Asian People / Q000235:genetics; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D005215:Fasting; D020022:Genetic Predisposition to Disease; D005941:Glucokinase / Q000235:genetics* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D011110:Polymorphism, Genetic; D017594:Publication Bias; D012306:Risk; D044465:White People / Q000235:genetics
chemical_list: D001786:Blood Glucose; D005941:Glucokinase; D005947:Glucose