Insulin receptor substrate-1 gene polymorphism in type 2 diabetes mellitus and essential hypertension : Association study and meta-analysis

To clarify the contribution of an amino acid substitution at codon 972 of insulin receptor substrate- 1 (IRS-1) causing a Gly to Arg change (Gly972Arg) to genetic susceptibility to insulin resistance and related diseases, we studied the association of the Gly972Arg polymorphism with type 2 diabetes and essential hypertension, both well-known insulin-resistant states. A total of 427 unrelated Japanese subjects (113 patients with type 2 diabetes, 110 patients with essential hypertension, 111 patients with type 2 diabetes and hypertension, and 93 healthy control subjects) were examined. The frequency of Arg allele was highest in patients with both type 2 diabetes and hypertension followed by patients with either one of these conditions, and lowest in subjects without these conditions (P=0.0375, Trend chi-squared test). By meta-analysis of data from the literature including our own data, summary odds ratio of Arg allele for type 2 diabetes was 1.26 (95% confidence interval: 0.93-1.71), with no evidence of heterogeneity among the studies. These results suggest the contribution of Gly972Arg polymorphism of the IRS-1 gene to genetic susceptibility to insulin-resistant state, such as type 2 diabetes and essential hypertension. The results of meta-analysis indicate that a larger scale study is necessary to confirm the hypothesis.