Genes coding for components of renin-angiotensin system and factors of endothelium and their role in development of diabetic nephropathy in type 2 diabetes mellitus
The given literature review highlights the current views of domestic and foreign authors on the role of genetic factors in development of diabetic nephropathy in type 2 diabetes mellitus, and pays attention to the role of candidate genes coding for components of renin-angiotensin system (ACE and AGT genes) and endothelial factors (eNOS3 and EDN 1 genes). The most widely investigated is the option associated with insertion or deletion of Alu-repeat in the 16th intron of ACE gene, and also polymorphism associated with a single nucleotide substitution of М235Т in AGT gene. Clinical practice proved that these RAS polymorphisms are the most important. The results of many-year research carried out in Russia and abroad were analyzed to establish associations between polymorphism in genes that determines endothelium factors, and development and progression of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus. Meta-analysis revealed association of three polymorphisms of eNOS3 gene with development of DN: 4b/a, T-786C and G984T. This allowed to conclude that eNOS3 gene plays a role in development of DN. The results of studies of the role of EDN 1 gene in development of DN still remain highly controversial and probably depend on the ethnic characteristics of the sample. Further study of the molecular basis of development and progression of renal pathology in diabetes mellitus is important for development of algorithms of early preclinical diagnosis and for elaboration of effective preventive measures and personalized predictive therapy.