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Article Type

Article

Subject Area

Clinical Pathology

Abstract

Background Insulin receptor substrate-1 gene (IRS-1) is an endogenous substrate of the insulin receptor present in insulin-sensitive tissues, allowing insulin signaling to take place. The IRS-1, rs1801278 gene with Gly972Arg substitution polymorphism is one of the most commonly studied variants in relation with type 2 diabetes mellitus (T2DM). Objective The objective of this study was to detect the genetic association of the IRS-1, rs1801278 gene polymorphism with secondary sulfonylurea (SU) failure and insulin resistance (IR) in T2DM in Egyptian patients. Patients and methods A total of 81 T2DM Egyptian patients (49 nonresponders and 32 responders to SU) were recruited. Genotyping of IRS-1, rs1801278 single nucleotide polymorphism was done using a TaqMan allelic discrimination assay with allele-specific designed fluorescent probes. Results Taking GG genotype and G allele as references, the genotypic and allelic frequency distribution of the IRS-1 Gly972Arg rs1801278 single nucleotide polymorphism showed a significant difference with GA + AA genotypes and A allele, being of higher frequency in the nonresponders group when compared with the responder group (odds ratio: 8.79; 95% confidence interval: 1.11–69.37) and in IR patients when compared with non-IR ones (odds ratio: 4.27; 95% confidence interval: 1.2–14.4). The association of the SU response with the presence or absence of IR showed a statistically significant difference, with more IR patients in the nonresponder group. Conclusion IRS-1 rs1801278 gene with Gly972Arg substitution polymorphism may be a significant genetic associate for SU efficacy and IR in Egyptian patients with T2DM.

Keywords

Insulin receptor substrate-1 gene, insulin resistance, sulfonylurea, type 2 diabetes mellitus

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