A study of the effect of gene polymorphism of xenobiotic biotransformation system, matrix metalloproteinases and interleukins on the development and course of distal neuropathy and diabetic foot syndrome in patients with type 1 and type 2 diabetes mellitus

Abstract

Aim to improve the effectiveness of early diagnosis, prediction and therapy of distal neuropathy (DN) and diabetic foot syndrome (DFS) in patients with type 1 and type 2 diabetes by identifying the features of gene polymorphism of xenobiotic biotransformation systems and antioxidant protection, pro- and anti-inflammatory cytokines.
 Material and methods. The study group included 150 patients aged from18 to 70 years, men and women with type 1 and type 2 diabetes, having DN and DFS, and 20 healthy people. Research methods used in the study: 1) clinical objective research; 2) molecular genetic methods; 3) population-statistics methods.
 Results. In patients with type 1 and type 2 diabetes with DN and DFS, the significant differences were found between the frequency of occurrence of polymorphism variants: G681A(*2) the CYP2C19 gene (2 = 9.642, p = 0.008), (OR = 0.334, (95% CI 0.145-0.768)); A8202G of the MMP9 gene (2 = 7.589, p = 0.022), (OR =0.476, (95% CI 0.226-1.005)); IIe105Val of the GSTP gene (2 = 19.521, p = 0.000), (OR = 0.174, (95% CI 0.070-0.435)); G-1293C(c1/c2) of the CYP2E gene (2 = 15.996, p = 0.000), (OR = 0.163, (95% CI 0.034-0.772)).
 Conclusion. Among patients suffering from type 1 and type 2 diabetes with the genotype A/A polymorphism G681A(*2) of the CYP2C19 gene, the DN and SDS are 4 times more likely to develop. The G/G polymorphism genotype A8202G of the MMP9 gene increases the risk of developing DN and DFS by almost 2 times. The genotype G/G polymorphism IIe105Val of the GSTP gene in patients increases the risk of developing DN and DFS by 4 times. The variant of the genotype C/C polymorphism G-1293C(c1/c2) of the CYP2E gene increases the risk of DN and DFS by 5 times.