Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) P22 Phox C242T gene polymorphism in type 1 diabetes.

Type 1 diabetes is caused by the immune-mediated destruction of insulin-secreting pancreatic beta cells and is thought to be an autoimmune disease resulting from a complex interaction of genetic and environmental factors. In animal models of type 1 diabetes, macrophages and their products, superoxides, have central roles in the beta cell destruction, but in humans their roles remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces superoxide in macrophages, and its essential component, p22 phox, is a critical enzyme for superoxide production. The C242T polymorphism in the p22 phox coding gene has been reported to be associated with reduced oxidase activity. We therefore investigated whether the p22 phox gene polymorphism affected the susceptibility to and clinical course of type 1 diabetes. We examined 287 Japanese type 1 diabetic patients and 425 unrelated nondiabetic subjects. In addition, we allocated the diabetic patients to the following three groups: (1) acute-onset type 1 diabetes with at least one autoantibody (GADA, IA-2, IAA); (2) acute-onset type 1 diabetes without autoantibodies; and (3) slow-onset type 1 diabetes with autoantibody. We could not find a significant difference in p22 phox genotype and T allele frequency between overall type 1 diabetic patients and control subjects. Regardless of the onset pattern and autoantibody positivity of type 1 diabetes, no difference in p22 phox genotype and T allele frequency was found among the groups. In conclusion, the p22 phox C242T gene polymorphism did not affect the susceptibility to and clinical course of Japanese type 1 diabetes.