Association between Superoxide Dismutase 2 p.(Ala16Val) and Superoxide Dismutase 3 p.(Arg213Gly) Genetic Variants and Risk of Peripheral Neuropathy in Children and Adolescents with Type 1 Diabetes

Abstract

Diabetic neuropathy (DN) is one of the microvascular complications of diabetes. Marked increase in oxygenfree radicals (OFR) results in oxidative stress that leads to development of DN. Antioxidant enzymes playa major role in protection against progression of DN, by reducing OFR. This study aimed to investigatethe association between superoxide dismutase 2 SOD2:p.(Ala16Val) and superoxide dismutase 3 SOD3:p.(Arg213Gly) genetic variants and the risk of neuropathy in Type 1 Diabetes children and adolescent. Thestudy included 80 children with type 1 diabetes divided into 2 groups, group 1 of 40 patients with clinicalDN and group 2 of 40 patients without DN. HbA1c levels were measured and genetic variants of SOD2:p.(Ala16Val) and SOD3:p.(Arg213Gly) were assessed by Taqman Real time Polymerase Chain Reaction(PCR) for both groups. The frequency of Ala/Ala genotype (OR=0.28 with 95% CI of 0.11-0.71) and Alaallele (OR=0.33 with 95% CI of 0.17-0.65) of SOD2:p. (Ala16Val) were significantly lower in group 1(27.5%, 50% respectively) than group 2 (57.5%, 75% respectively) (p=0.007, p=0.001 respectively). Incontrast the frequency of Val/Val genotype (OR=4.68 with 95% CI of 1.19-18.3) and Val allele (OR=3 with95% CI of 1.54-5.86) were significantly higher in group 1 (27.5%, 50% respectively) than group 2 (7.5%,25% respectively) (p=0.019 and p=0.001 respectively). Regarding SOD3:p.(Arg213Gly) gene variants thefrequency of Arg/Arg genotype and Arg allele were higher in group 1 (100%,100% respectively) than group2 (90%,95% respectively) but with statistical insignificance (P=0.06, P=0.058 respectively), however thefrequency of Arg/Gly genotype and Gly allele were higher in group 2 (10%, 5% respectively) than group 1(0%, 0% respectively) but also with no statistical significance (P=0.058 and P=0.06 respectively). There isa possible association between SOD2:p.(Ala16Val), but not with SOD3:p.(Arg213Gly) genetic variants andthe occurrence of DN in patients with type 1 diabetes mellitus.