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Background:  Insulin Receptor Substrate (IRS) molecules play a major role in insulin signalling, and single nucleotide polymorphisms in the IRS-1 (rs1801278) and IRS-2 (rs1805097) gene has been associated with the predisposition to the development of type-2 diabetes (T2D) in some population. However, the observations remain contradictory. Discrepancies in the results have been attributed to several factors, and consideration of a smaller sample size is one of them. To reach a valid conclusion, we performed a meta-analysis of the genetic association between IRS-1 (rs1801278) and IRS-2 (rs1805097) polymorphism with a predisposition to T2D.  Materials and Methods:  The literature search was performed in different databases such as PubMed, Science Direct, and Scopus. All relevant articles were screened and based in inclusion and exclusion criteria eligible reports were identified. Baseline characteristics, genotype and allele frequencies were extracted from the eligible reports. The meta-analysis was performed by comprehensive meta-analysis software v3.3.070 and odds ratios, 95% confidence interval and probability values were calculated to find out association of IRS-1 and IRS-2 polymorphisms with rhinitis.  Results:  A total of seven studies comprising 1287 cases and 1638 control were considered for the present meta-analysis for the association of IRS-1 (rs1801278) polymorphism with T2D, and no significant association was observed. For IRS-2 (rs1805097) polymorphism, data from eight cohorts (cases: 1824, controls: 1786) were considered. The heterozygous genetic comparison models revealed a significant protective association against T2D predisposition ( p  = 0.017, OR = 0.841, 95% CI = 0.729 to 0.970). The trial sequential analysis revealed the requirement of additional case-control studies to draw a definitive conclusion for IRS-1 polymorphism.  Conclusions:  IRS-2 rs1805097 heterozygotes are protected from T2D development. However, IRS-1 (rs1801278) is not associated with a subject’s proclivity for T2D.

Association of IRS-1 and IRS-2 polymorphisms with predisposition to type-2 diabetes (T2D): a meta-analysis and trial sequential analysis