Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with iron status in persons with type 2 diabetes mellitus

Background: High iron stores are known to cause type 2 diabetes mellitus in persons with hemochromatosis. However, it is not clear whether moderately elevated iron stores predict the risk of type 2 diabetes in healthy persons. Heme oxygenase (HO) I expression is increased when intracellular iron increases. Furthermore, HO shows a microsatellite polymorphism in its gene promoter that could be related to its expression and activity. Objectives: We aimed to determine the length of (GT)(n) repeats in the HO1 gene promoter by using capillary electrophoresis and HO enzymatic activity in mononuclear cells (MNCs) from adult diabetes patients. We also aimed to assess the relation between these results and iron stores. Design: We studied 99 patients with type 2 diabetes mellitus and 90 nondiabetic (control) subjects. We determined iron status (serum iron, ferritin, and transferrin receptor), HO activity, and micropolymorphism. Results: One diabetes patient and 5 control subjects had iron deficiency anemia. No iron overload was detected in either group. Diabetes patients had significantly greater iron stores (P < 0.0001), total body iron (P < 0.001), and HO activity (P < 0.001) than did control subjects. A positive association between serum iron and HO activity was seen in the diabetes patients (P < 0.0001). Allelic frequency did not differ significantly between diabetes patients and control subjects; however, the frequency of the SM genotype was significantly higher and that of the SS and MM genotypes was significantly lower in the diabetes patients than in control subjects (P < 0.001 for all). Conclusions: Type 2 diabetes patients carrying short (GT), repeats may have higher ferritin values and greater HO enzymatic activity and may have greater susceptibility to diabetes than may those with long (GT)n repeats.