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 oxygen
free radicals (OFR) results in oxidative stress that leads to development of DN. Antioxidant enzymes play
a major role in protection against progression of DN, by reducing OFR. This study aimed to investigate
the 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. The
study included 80 children with type 1 diabetes divided into 2 groups, group 1 of 40 patients with clinical
DN 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 Ala
allele (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). In
contrast the frequency of Val/Val genotype (OR=4.68 with 95% CI of 1.19-18.3) and Val allele (OR=3 with
95% 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 the
frequency of Arg/Arg genotype and Arg allele were higher in group 1 (100%,100% respectively) than group
2 (90%,95% respectively) but with statistical insignificance (P=0.06, P=0.058 respectively), however the
frequency 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 is
a possible association between SOD2:p.(Ala16Val), but not with SOD3:p.(Arg213Gly) genetic variants and
the occurrence of DN in patients with type 1 diabetes mellitus.