Abstract
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.
Highlights
Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder which manifests a heterogeneous group of metabolic diseases
Implication for health policy/practice/research/medical education: The present meta-analysis showed a significant relationship between GA genotype of Gly1057Asp polymorphism and type 2 diabetes mellitus (OR=0.88; 95% confidence interval, 0.79-0.98), whereas no significant relationship between GG and AA genotype with type 2 diabetes mellitus was seen; odds ratios (ORs) for GG and AA genotypes were 1.10 and 1.13, respectively
The present meta-analysis from nine published articles does not find a significant relationship between Gly1057Asp polymorphisms and the increased risk of T2DM
Summary
Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder which manifests a heterogeneous group of metabolic diseases. Glucose intolerance is the common feature of T2DM, and resulting from by at least two pathophysiological defects: impaired insulin signaling and failure of pancreatic β cells to compensate for poor insulin action through an appropriate increase of insulin secretion [1,2]. Kiani F et al insulin receptors in both liver and pancreatic beta cells, which play a part in underlying pathogenesis of the type 2 diabetes [4,5]. Given to its crucial role in the insulin signaling system and in development and/or survival of pancreatic beta cell, it may be an attractive candidate in the pathogenesis of type 2 diabetes [6]. It has been shown that IRS-2 protein as a key mediator in insulin signaling plays a central role in insulin-dependent cellular functions such as growth, survival, and metabolism [7]
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