Genetic association of insulin receptor substrate-1 (IRS-1, rs1801278) gene with insulin resistant of type 2 diabetes mellitus in a Pakistani population

Insulin resistance (IR), a pathological condition of type 2 diabetes mellitus (T2DM) is characterized by an inability of body’s tissue to respond the secreted or administered insulin, a necessary step for cellular glucose transportation. The prevalence of insulin resistance progresses with age, especially in overweight people with central obesity. Insulin receptor substrates (IRS) are important molecular proteins in the insulin signalling pathway, where IRS-1 plays a key function in cells insulin sensitivity. The common mutation (rs1801278; r.2963G > A: Gly972Arg) of the IRS-1 gene occurs when residue glycine changes to arginine at codon 972. The objective of this study was to detect the genetic association of rs1801278 polymorphism of the IRS-1 gene with insulin resistance in type 2 diabetes from the Lahore region of Pakistan. A total of 322 subjects (161 cases and 161 healthy individuals) were included. DNA was isolated for detection of the genotype distribution and allele frequencies by PCR–RFLP. The results showed a significant difference in the genotype distribution and allele frequency between the T2DM cases and controls for single nucleotide polymorphism (SNP) rs1801278 (OR 17.61, 95% CI 8.06–38.4, p < 0.001). In conclusion, association between rs1801278 polymorphism of the IRS-1 gene and insulin resistance in T2DM has been established in a Pakistani population.