Extracellular superoxide dismutase gene polymorphism is associated with insulin resistance and the susceptibility to type 2 diabetes

We identified two missense mutations, Ala40Thr (GCG → ACG) and Arg213Gly (CGG → GGG), and a silent mutation, Leu53Leu (CTG → TTG). For one of these variants, the Ala40Thr polymorphism, the frequency of Thr allele and the number of subjects with Thr allele (Ala/Thr + Thr/Thr) were higher in type 2 diabetic patients (n = 205) than those in non-diabetic subjects (n = 220) (33.2% versus 24.1%, p = 0.003 and 55.6% versus 42.7%, p = 0.008, respectively). The patients with Thr allele also showed earlier age at diagnosis of diabetes (42.2 ± 7.8 years versus 44.4 ± 6.9 years, p = 0.037) and higher prevalence of hypertension (53.5% versus 38.5%, p = 0.032) than those without the allele. Insulin sensitivity, furthermore, was evaluated in 71 type 2 diabetic patients with short insulin tolerance test (SITT). The patients with Thr allele showed lower insulin sensitivity (Kitt value of SITT) than those without the allele (1.78 ± 0.78%/min versus 2.33 ± 1.02%/min, p = 0.012), although no significant differences in other clinical and biochemical characteristics were observed between two groups. These results suggest that the genetic variant of EC-SOD gene is associated with insulin resistance and the susceptibility to type 2 diabetes.