title: Large scale meta-analyses of fasting plasma glucose raising variants in GCK, GCKR, MTNR1B and G6PC2 and their impacts on type 2 diabetes mellitus risk.
abstract: BACKGROUND
  The evidence that the variants GCK rs1799884, GCKR rs780094, MTNR1B rs10830963 and G6PC2 rs560887, which are related to fasting plasma glucose levels, increase the risk of type 2 diabetes mellitus (T2DM) is contradictory. We therefore performed a meta-analysis to derive a more precise estimation of the association between these polymorphisms and T2DM.
  
  
  METHODS
  All the publications examining the associations of these variants with risk of T2DM were retrieved from the MEDLINE and EMBASE databases. Using the data from the retrieved articles, we computed summary estimates of the associations of the four variants with T2DM risk. We also examined the studies for heterogeneity, as well as for bias of the publications.
  
  
  RESULTS
  A total of 113,025 T2DM patients and 199,997 controls from 38 articles were included in the meta-analysis. Overall, the pooled results indicated that GCK (rs1799884), GCKR (rs780094) and MTNR1B (rs10830963) were significantly associated with T2DM susceptibility (OR, 1.04; 95%CI, 1.01-1.08; OR, 1.08; 95%CI, 1.05-1.12 and OR, 1.05; 95%CI, 1.02-1.08, respectively). After stratification by ethnicity, significant associations for the GCK, MTNR1B and G6PC2 variants were detected only in Caucasians (OR, 1.09; 95%CI, 1.02-1.16; OR, 1.10; 95%CI, 1.08-1.13 and OR, 0.97; 95%CI, 0.95-0.99, respectively), but not in Asians (OR, 1.02, 95% CI 0.98-1.05; OR, 1.01; 95%CI, 0.98-1.04 and OR, 1.12; 95%CI, 0.91-1.32, respectively).
  
  
  CONCLUSIONS
  Our meta-analyses demonstrated that GCKR rs780094 variant confers high cross-ethnicity risk for the development of T2DM, while significant associations between GCK, MTNR1B and G6PC2 variants and T2DM risk are limited to Caucasians.
authors.affiliation: Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Jinzhao
authors.initials: J
authors.lastname: Zhao
authors.forename: Guanglin
authors.initials: G
authors.lastname: Cui
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Hu
authors.initials: H
authors.lastname: Ding
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005215:Fasting; D020022:Genetic Predisposition to Disease / Q000235:genetics; D000081410:Germinal Center Kinases; D005952:Glucose-6-Phosphatase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D044122:Receptor, Melatonin, MT1 / Q000235:genetics* / Q000378:metabolism; D044123:Receptor, Melatonin, MT2; D012306:Risk; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; C485100:GCKR protein, human; D000081410:Germinal Center Kinases; C573871:MTNR1B protein, human; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D017346:Protein Serine-Threonine Kinases; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human