The 262T>C promoter polymorphism of the catalase gene is associated with diabetic neuropathy in type 1 diabetic Russian patients

Objective: Oxidative stress plays an important role in the development of diabetic neuropathy (DN). Antioxidant enzymes reduce enchanced oxidative stress in the peripheral nerve. Genetic variations within the antioxidant genes therefore could be implicated in the pathogenesis of ON. Methods: Using a PCR-RFLP assay, a total of 216 Russian type 1 diabetic (T1D) patients with ON and 250 T1D individuals without ON have been tested to verify whether the -262T > C and 1167C > T polymorphisms of the catalase (CAT), 197Pro > Leu amino acid substitution of the glutathione peroxidase 1 (GPX1) and +/null polymorphism of the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes contribute to susceptibility to ON. Results: Association between the -262T > C polymorphism of the CAT gene and ON was shown. The -262TT genotype of the CAT gene was significantly associated with higher erythrocyte catalase activity in blood of ON patients compared to the -262CC genotype (17.8 +/- 2.7 x 10(4) lU/g Hb vs. 13.5 +/- 3.2 X 10(4) IU/g Hb, P = 0.0022). Conclusions: These data suggest a protective role of the -262T allele of the CAT gene against the rapid development of DN in T1 D (Odds Ratio = 0.7 [95% confidence interval 0.54-0.9], P = 0.002).