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Surveying the relationship between Gly1057Asp polymorphism of IRS-2 gene and susceptibility to type 2 diabetes; a systematic review and meta-analysis study

Type 2 diabetes mellitus (T2DM) is a multi-factorial disease in which influenced by several genetic and environmental factors. Insulin receptor substrate 2 (IRS 2) is the main mediator of insulin in the liver which controls insulin sensitivity. Gly1057Asp polymorphism is one of the candidates to increase risk of T2DM. The present study is an attempt to study the relationship of Gly1057Asp polymorphism of IRS-2 and T2DM by a meta-analysis. A systemic search was conducted in English and Persian databases such as Scopus, PubMed, Google Scholar, SID, and other academic databases for studies that have investigated the relationship of Gly1057Asp polymorphism of IRS-2 and T2DM. This association was determined using odds ratios (ORs) with a confidence interval of 95% (CIs). Heterogeneity of the studies was examined by I2 index. Funnel plots and Egger tests were used to determine bias or publication bias. The collected data was analyzed in STATA through meta-analysis. Nine articles were selected as eligible for further analysis, which represented 3,196 patients with T2DM and 3409 controls subjects without T2DM. The present meta-analysis showed a significant relationship between GA genotype of Gly1057Asp polymorphism and T2DM (OR=0.88; 95% confidence interval, 0.79-0.98), whereas no significant relationship between GG and AA genotype with T2DM was seen; OR for GG and AA genotypes were 1.10 (95% CI, 0.99 -1.22) and 1.13 (95% CI, 0.95- 1.33), respectively. The results of our study show that genotype GA of Gly1057Asp polymorphism of IRS-2 gene plays a protective role and may decrease the risk of T2DM, whereas GG and AA genotypes are considered as a risk factor and related to development of T2DM to some extents.