An analysis of the association between a polymorphism rs5219 of KCNJ11 and GFR in CKD development in patients with type 2 diabetes in Russian population

Abstract

Background. Chronic kidney disease is one of the most serious diabetic complications, which end-stage leads to a dramatic decline of renal function and needs for renal replacement therapy. Due to the progressive nature of CKD and the limited efficacy of treatment for advanced stages the prediction of risks and diagnostics on preclinical stage are of great importance. All of the above determines the high relevance of search for genetic markers predict the chronic kidney disease (CKD) development.The aim of our study was to investigate association between polymorphic marker (PM) of gene involved in insulin secretion with development of CKD in type 2 diabetic (T2D) patients. Polymorphism of KCNJ11 gene is associated with different phenotypes of glycemic disorders: neonatal diabetes, hyperinsulinemia, reduced insulin secretion and increased risk of type 2 diabetes. This gene coding Kir6.2 subunit of ATP-dependent potassium channels. The pathogenesis of it’s involvement in renal damage development referred to the fact that this type of potassium channels found not only in the beta- cells, but also in smooth muscle cells of blood vessels, and therefore might have an effect on risk of vascular complications, including CKD.Materials and methods. We enrolled 444 T2D patients. PM rs5219 in KCNJ11 gene was analysed among patients divided in 2 groups: with and without CKD (n=123/321) based on glomerular filtration rate (GFR) < and ≥ 60 ml/min/1,73m2 calculated by MDRD formula. PM studied using PCR. Differences in alleles/genotypes frequencies were assessed by χ² and odds ratio (OR) were calculated. The study was approved by local ethical committee; informed concern was obtained from all the patients.Results. We studied the main clinical parameters: age, HbA1c, serum levels of cholesterol and triglycerides, BP between the groups. We observed significant differences in alleles/genotypes distribution of rs5219 in KCNJ11 gene between groups with and without CKD: the prevalence of allele C and genotype CC in patients without CKD: OR=0,53, 95%CI: 0,40-0,72 and OR=0,46, 95%CI: 0,27-0,79, respectively; while allele T and genotype TT did as risk factors: χ²=17,33; р=0,0002; OR=1,87, 95%CI: 1,39-2,53; genotype TT OR=2,39, 95%CI: 1,52-3,76.Conclusions. We conclude that T2D patients might have genetic susceptibility to CKD development caused by polymorphism rs5219 of KCNJ11 gene with protective role of allele C and genotype CC and risk allelе/genotype is T/TT.