MICROANGIOPATHIC COMPLICATIONS RELATED TO DIFFERENT ALLELES OF MANGANESE SUPEROXIDE DISMUTASE GENE IN DIABETES MELLITUS TYPE 1

Oxidative stress, resulting from the imbalance between prooxidant and antioxidant states, damages DNA, proteins, cell membranes, and mitochondria and seems to play a role in the etiology of diabetic microangiopathic complications as diabetic neuropathy (DN) and nephropathy (DP). Antioxidant enzymes may protect against the rapid onset and progression of microangiopathy, by reducing the excess of oxygen free radicals, and peroxides. Mutations and polymorphisms in the genes encoding such enzymes may therefore result in predisposition to these disorders. In this study the role of genes encoding antioxidant enzyme, mitochondrial superoxide dismutase (Mn-SOD2), in DN and DP pathogenesis in Egyptian population were investigated. Ala (-9) Val polymorphism of the Mn-SOD2 gene in type 1 diabetic patients without complications (n = 61) and with DN (n = 36) or with DP (n = 42) was studied.A new polymerase chain reaction (PCR) assays with restriction fragment length polymorphism (RFLP) for rapid detection of polymorphisms was used. These assays involved the use of mismatch PCR primers to create restriction sites in the amplified product only in the presence of the polymorphic base. The PCR product was then digested with Age I restriction enzyme, to detect Ala (-9) Val, polymorphic site. The frequencies of the Ala allele (odds ratio= 0.445 with 95% CI of 0.243- 0.755) and the Ala/Ala genotype (odds ratio= 0.248 with 95%CI of 1.37- 10.162) were significantly low (p 0.05) in diabetic neuropathy, patients. In contrast, the Val allele (odds ratio= 2.232 with 95%CI of 1.268- 4.053) and the homozygous Val/Val genotype (odds ratio= 6.23 with 95%CI of 0.31- 0.79) were significantly higher (P 0.05) in patients with DN than diabetics without neuropathy. Although the Val/Val genotype frequency was more in DP patients than diabetics without nephropathy (odds ratio= 3.05). This difference was statistically non-significant (p 0.05). In conclusion, Ala (-9) Val substitution in the Mn-SOD2 gene was associated with diabetic neuropathy with non-significant change in diabetic nephropathy in type I diabetic Egyptian pateints.