Association of IRS1 genetic variants with glucose control and insulin resistance in type 2 diabetic patients from Bosnia and Herzegovina

Previous studies reported conflicting results regarding association of insulin receptor substrate 1 (IRS1) gene variation with type 2 diabetes (T2D) and insulin resistance (IR) in different ethnic groups. We examined the association of rs7578326, rs2943641, and rs4675095 in the IRS1 gene with T2D and related traits in a population from Bosnia and Herzegovina, which is one of the European countries with the highest T2D prevalence of 12.5%. Our study included 390 T2D patients and 252 control subjects. Biochemical parameters, including fasting glucose (FG), fasting insulin (FI), homeostasis model assessment insulin resistance index (HOMA-IR), and HbA _1c were measured in all participants. Genotyping analysis was performed by Mass Array Sequenom iPlex platform. Our results demonstrated that rs7578326 and rs4675095 variants were associated with increased FG levels. The rs7578326 was also associated with higher FI, HOMA-IR (B = 0.08, 95% CI [0.01, 0.15], p _add = 0.025; B = 0.079, 95% CI [0.006, 0.150], p _add = 0.033, respectively) in T2D, and with HbA _1c (B = 0.034, 95% CI [0.003, 0.065], p _dom = 0.035) in non-drug-treated T2D. In contrast, rs2943641 C allele was associated with lower FG levels in control subjects (B = -0.17, 95% CI [-0.03, -0.002], p _add = 0.030) and HbA _1c (B = 0.03, 95% CI [0.002, 0.06], p _dom = 0.040) in non-drug-treated T2D. We report the association between common variants in IRS1 gene with insulin resistance, glucose, and HbA _1c levels in Bosnia and Herzegovina's population.