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Effect of Interaction between Polymorphisms in Insulin Receptor Substrate Genes in Type 2 Diabetes Mellitus Patients with Severe/Acute Hyperglycemia Huri, Hasniza Zaman; Makmor-Bakry, Mohd; Hashim, Rosnani; Mustafa, Norlaila & Ngah, Wan Zurinah Wan Abstract Purpose: To investigate whether there are interactions between insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) that are associated with increased insulin resistance during such episodes. Methods: Testing Haplotype EffectS in Association Studies (THESIAS) software was used to investigate allelic and haplotype interactions between the polymorphisms in 156 T2DM patients with severe or acute hyperglycemia. Results: Binary analysis showed there were significant differences in the haplotype frequencies for the IRS1 and IRS2 polymorphisms based on the insulin resistance status. Nevertheless, estimation of haplotype effects by equality analysis showed no significant interactions (likelihood ratio tests: all p > 0.05) in increased insulin resistance in T2DM patients with severe/acute hyperglycemia. Conclusion: There are no interactions between IRS1 rs1801278 (p.Gly972Arg) and IRS2 rs1805097 (p.Gly1057Asp) polymorphisms that would affect insulin resistance in T2DM patients with severe/acute hyperglycemia. Keywords Insulin receptor substrate; Proteins; Insulin resistance; Diabetes mellitus; Hyperglycemia; Haplotype; Genetic polymorphism

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