Features of prooxidant/antioxidant balance disorders in patients with diabetic nephropathy — carriers of different genotypes of G894T polymorphism of eNOS gene

Abstract

Objective — to determinate the state of prooxidant‑antioxidant balance in patients with type 2 diabetes mellitus with nephropathy — carriers of different genotypes of G894T (rs 1799983) polymorphism of eNOS gene. Materials and methods. 126 patients with diabetic nephropathy (DN) were examined. The control group included 20 healthy individuals. Patients with type 2 diabetes mellitus (DM) were divided into two groups depending on the eNOS rs 1799983 gene polymorphism: group I — patients with DN and G/G genotype eNOS G894T gene (n=80); group II — patients with DN and G/T and T/T genotypes eNOS G894T gene (n=46). Results. The distribution of genotypes of the rs1799983 polymorphism of the eNOS gene corresponded to the Hardy‑Weinberg equilibrium. Data analysis demonstrated a significant difference in the frequency of occurrence of genotypes and alleles of the studied polymorphism in the group of patients with DN compared with controls, which corresponds to the dominant model of inheritance (odds ratio 0.31 (95% confidence interval 0.09—0.99), p=0.045). There were significant gender differences in the frequency of genotypes and alleles of the studied polymorphism in the group of patients with type 2 DM with DN: women had a significantly lower risk of the G/T polymorphism genotype than men. The study of total antioxidant activity (TAA) revealed significantly lower values of this parameter in patients with G/G genotype of the rs1799983 polymorphism of the eNOS gene compared to carriers of the T allele (G/T+T/T genotypes). In diabetic patients with different genotypes of the rs1799983 polymorphism of the eNOS gene, the levels of total hydroperoxides (THP) did not differ significantly. Homozygous and heterozygous carriers of the T allele of the rs1799983 polymorphism of the eNOS gene had a significant increase in the prooxidant‑antioxidant balance. Conclusions. In patients with DN, the distribution of genotypes of the G894T polymorphism (rs 1799983) of the eNOS gene corresponds to the Hardy‑Weinberg equilibrium in all studied groups and does not differ significantly from European populations. In men, the risk of having a heterozygous G/T genotype of the G894T (rs 1799983) polymorphism of the eNOS gene is 3 times higher than in women (according to the dominant model of inheritance, odds ratio 0.41 (95% confidence interval 0.20—0.83), p=0.013). In carriers of G/T and T/T genotypes, a significant increase in prooxidant‑antioxidant balance was observed against the background of a decrease in total antioxidant activity, compared with carriers of G/G genotype (p<0.05).