Manganese Superoxide Dismutase Alanine to Valine Polymorphism and Risk of Neuropathy and Nephropathy in Egyptian Type 1 Diabetic Patients

Oxidative stress, characterized by a marked increase in the level of oxygen free radicals (OFR), has been implicated in the development of diabetic microangiopathic complications, such as diabetic neuropathy (DN) and nephropathy (DP). Antioxidant enzymes may protect against the rapid onset and progression of microangiopathy, by reducing the excess of OFR and peroxides. Mutations and polymorphisms in genes encoding such enzymes may therefore result in a predisposition to this disorder. Aim: we investigated the role of genes encoding the antioxidant enzyme, mitochondrial superoxide dismutase (Mn-SOD2), in DN and DP pathogenesis in an Egyptian population. We studied Ala(-9)Val polymorphism of the Mn-SOD2 gene in type 1 diabetic patients (n = 65) with DN (n = 40) or DP (n = 45). Methods: we used polymerase chain reaction (PCR) assays with restriction fragment length polymorphism for rapid detection of polymorphisms. These assays involved the use of mismatch PCR primers to create restriction sites in the amplified product only in presence of the polymorphic base. The PCR product was then digested with AgeI restriction enzyme to detect Ala(-9)Val polymorphic sites. Results: the frequencies of the Ala allele (odds ratio (OR) = 0.438, 95% CI of 0.247 - 0.778) and the Ala/Ala genotype (OR = 0.26, 95% CI of 1.39 - 10.266) were significantly lower in diabetic neuropathy patients. In contrast, the frequencies of the Val allele (OR = 2.282, 95% CI of 1.286 - 4.05) and the homozygous Val/Val genotype (OR = 6.68, 95% CI of 0.3 - 0.76) were significantly higher in patients with DN than diabetics without neuropathy. Although the Val allele was more frequently detected in DP patients than diabetics without nephropathy (OR = 3.2), this difference was statistically non-significant. In conclusion, Ala(-9)Val substitution in the Mn-SOD2 gene was associated with DN in Egyptian diabetic children but not a significant factor in diabetic patients with nephropathy.