[The genetic and biochemical mechanisms of the development of diabetic nephropathy in children].

The mechanisms responsible for the development of microangiopathies in type diabetes mellitus (DM1) are complex and under extensive study. Fresh data on the pathogenesis of DM1 make it possible to direct actual ways to the studies aimed at preventing the complications of this disease. The purpose of this study was to examine the contribution of the polymorphic types of the VNTR polymorphism of endothelial NO-synthase gene (NOS3) and the I/D polymorphism of angiotensin-converting enzyme (ACE), the status of the proteolytic systems and lipid metabolic disturbances to the development of diabetic neuropathy (DN). A total of 197 children Работа выполнена при финансовой поддержке гранта РГНФ № 00-06-00- 162а. who had DM1 in 1996-2002 were examined. Their mean age was 13.1 ±0.3 years. A control group comprised 32 apparently healthy children whose mean age was 12.8±0.1 years. DN was present in 44 children (19 boys and 25 girls). It has been established that allele A of endothelial NO-synthase is less common in diabetic patients with nephropathy (p < 0.05) and that it is a factor that reduces, while insignificantly, the risk for nephropathy (RR = 0.13). Analyzing the association with pathology by using the transmission/disequilibrium test has indicated the association of allele В of the gene NOS3 (TDT = 4.5, p - 0.034) and allele D of the gene ACE (TDT = 3.6, p < 0.05) with DN. The activity of plasma kallikrein was increased at the early stages of nephropathy (hyper-function). The higher activity of angiotensin-converting enzyme (57.0±2.9 µmol/min·l in the patients with nephropathy versus 38.1±2.8 µmol/min·/ in those without this disease) and the substantial suppression of α-proteinase inhibitor (21.1+-1.2 IU/ml in nephropathy at the stage of proteinuria versus 27.6±1.6 IU/ml without nephropathy) make a contribution to the development of nephropathy at the stages of microalbuminuria and proteinuria. ffyperlipidemia that manifests itself by the increased levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol and by the decreased levels of high-density lipoprotein cholesterol is one of the mechanisms responsible for the development of DN in DM1.