Genetic Polymorphism of Endothelial Nitric Oxide Synthase (ENOS) and its Relationship to Diabetic Nephropathy in Children

Abstract

Background:Diabetic kidney disease (DKD) is defined as kidney disease attributed to diabetes. Diabetic nephropathy (DN) is a common micro vascular complication of diabetes .DN develops in 15-20% of subjects with T1DM and in similar or higher percentage of T2DM patients, causing increased morbidity and premature mortality. American Diabetes Association (ADA) recommends screening for nephropathy 5 years after diagnosis for type 1 diabetes and at diagnosis for type 2 diabetes.DN occurs in 20-40% of patients with diabetes and considered as a major cause of end-stage renal disease (ESRD). Kidney failure and overt DN caused by either type of diabetes are very uncommon during childhood or adolescence, but in susceptible T1DM patients, diabetic kidney disease almost certainly begins just after diagnosis and may accelerate during adolescence. Thus, all diabetics need ongoing assessment of kidney function and screening for earliest manifestation of renal injury. Micro albuminuria, or incipient DN is the most common abnormal finding in diabetic children and adolescents, although overt proteinuria is found in less than 1–1.5% of pediatric patients.ENOS gene has been considered a potential candidate gene to DN susceptibility. Since 1998, several polymorphisms of the eNOS gene have been identified, and their association with various diseases has been explored. Some of these polymorphisms are associated with reduction of either eNOS activity or plasma concentrations. Three polymorphisms have been the subject of research in relation to DN, however the results are highly variable. The polymorphism which potentially associated with DN is G894T missense mutation in exon 7 (rs1799983).