title: Association of the G1057D polymorphism in insulin receptor substrate 2 gene with type 2 diabetes mellitus: a meta-analysis.
abstract: OBJECTIVE
  The G1057D polymorphism in insulin receptor substrate (IRS)-2 gene is associated with type 2 diabetes mellitus (T2DM) risk, but results in published literatures are controversial. In addition, the effect of obesity as a modifier on this association is also inconsistent. Thus, this meta-analysis was performed to assess the above-mentioned association.
  
  
  METHODS
  A comprehensive search was performed to identify case-control or cohort studies (from 1990 to 2014) of the aforementioned association. The I(2) statistic was used to examine between-study heterogeneity. Fixed or random effect model was selected based on heterogeneity test among studies. Publication bias was estimated using modified Egger's regression test.
  
  
  RESULTS
  Nine articles with ten studies were included. After excluding studies deviated from Hardy-Weinberg equilibrium (HWE) in controls, results showed a significant association of D allele with reduced T2DM risk in dominant (OR = 0.825, 95% CI: 0.705-0.965) and codominant (OR = 0.857, 95% CI: 0.763-0.964) models, but no significant association in recessive (OR = 0.806, 95% CI: 0.628-1.035) model. For studies stratified by obesity, after excluding studies deviated from HWE in controls, no significant association of D allele with T2DM risk was found in three inherited models in obese group; however, a significant protective effect of D allele was observed in dominant (OR = 0.714, 95% CI: 0.533-0.958), recessive (OR = 0.438, 95% CI: 0.253-0.760) and codominant (OR = 0.706, 95% CI: 0.565-0.883) models in non-obese group.
  
  
  CONCLUSIONS
  This meta-analysis suggested that D allele of G1057D polymorphism have a significant effect on reduced risk of T2DM, and obesity is a modifier of this association. This result needs to be confirmed by further studies.
authors.affiliation: Department of Epidemiology and Biostatistics, Shandong University, P. R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Epidemiology and Biostatistics, Shandong University, P. R. China.
authors.forename: Suyun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, Shandong University, P. R. China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Epidemiology and Biostatistics, Shandong University, P. R. China. Electronic address: jiachongqi@sdu.edu.cn.
authors.forename: Chongqi
authors.initials: C
authors.lastname: Jia
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D009765:Obesity / Q000150:complications; D020641:Polymorphism, Single Nucleotide
chemical_list: C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins
keywords: Diabetes; G1057D; IRS-2; Meta-analysis; Polymorphism