РОЛЬ ПОЛИМОРФИЗМОВ ГЕНОВ СИСТЕМЫ БИОТРАНСФОРМАЦИИ КСЕНОБИОТИКОВ И АНТИОКСИДАНТНОЙ ЗАЩИТЫ В РАЗВИТИИ ДИАБЕТИЧЕСКОЙ НЕФРОПАТИИ

Abstract

Introduction.The main etiopathogenetic mechanisms of the development of multifactorial diseases are genetic predisposition and environmental factors. A special role in the prognosis of type 1 diabetes mellitus is played by diabetic nephropathy, which leads to chronic kidney disease in its outcome. In the conditions of modern technogenic civilization, it is believed that the most significant contribution to the formation of predisposition to socially significant human diseases can be made by genes of enzymes of protective and adaptive systems of the body – these are, first of all, genes of enzymes of antioxidant protection and biotransformation of xenobiotics. The aim of the study was to study the role of polymorphic variants of genes of the xenobiotic biotransformation system and antioxidant protection (G681A in the CYP2C19 gene; G1293C in the CYP2E1 gene) in the development of diabetic nephropathy in patients with type 1 diabetes mellitus. Material and methods. The study included patients with type 1 diabetes mellitus (50 people) and healthy individuals (20 people). Molecular-genetic, clinical-laboratory and biochemical research methods were used. The reliability of differences in the distribution of genotype frequencies between groups of patients and healthy individuals was assessed by the test2, by the method of conjugate tables (four-field table). Results and discussion. The activity of the processes of free radical oxidation and lipid peroxidation increases many times in type 1 diabetes mellitus, which is confirmed in our study by an increase in the content of malondialdehyde products against the background of an increase in the activity of enzymes of the antioxidant defense system. This is especially evident in individuals carrying heterozygous polymorphism of the CYP2C19 (G681A) and CYP2E1 (G1293C) genes, which is also combined with a more pronounced decrease in kidney function in these patients compared with carriers of other polymorphic variants of the studied genes. Conclusion. Heterozygous polymorphism of the CYP2C19 (G681A) and CYP2E1 (G1293C) genes in combination with increased activity of antioxidant defense enzymes and xenobiotic biotransformation enzymes leads to a more severe course of diabetic nephropathy in patients with type 1 diabetes mellitus.