Association Analyses Of Genetic Variants For Diabetic Nephropathy In TianJin Population With Type2Diabetes

Objective:Diabetic nephropathy, a major microvascular complication of both type1diabetes mellitus (T1DM) and type2diabetes mellitus (T2DM), is an important cause of end-stage renal disease. This complication was traditionally thought to result from interactions between hemodynamic and metabolic factors.However, current knowledge indicates that the extent of renal damage in patients with diabetes mellitus is not completely explained by increased systemic and intraglomerular pressure secondary to hemodynamic and metabolic factors, or by the modification of molecules under hyperglycemic conditions. Clear evidence indicates that the pathogenesis of diabetic nephropathy is multifactorial; both genetic and environmental factors are responsible for triggering a complex series of pathophysiological events.16SNPs loci of nine genes associated with the podocyte barrier,inflammation,hemodynamics and epithelial-mesenchymal transformation were examined and performed the association analysis so as to explore the role of gene interaction in diabetic nephropathy.Method:A total of1329patients with type2diabetes whose nationality is all Han were collected, they were from the Tianjin Medical University General Hospital, Metabolic Diseases Hospital, Nankai University People’s Hospital.Collect the patient’s general information and clinical biochemical parameters, including age, weight, blood glucose, serum creatinine, albumin and other clinical datas. According to the patients with or without the complication of DN, they were divided into two groups:diabetic nephropathy group and non-diabetic nephropathy group. Patients in non-DN group whose diabetes history longer then10years as controls. Genomic DNA were extracted from peripheral leukocytes using DNA Extraction Kit (Ping Hao kit). The16SNPs loci of nine genes in type2diabetic patients were genotyped using desorpte ionization time of flight mass spectrometry matrix-assisted laser. The data were analyzed with SPSS16.0software. Penotype-phenotype correlation and genotype interaction were analyzed with PLINK software.Result:1. As compared with controls,rs1526167and rs17304270SNP loci of TOX gene, rs12102171SNP loci of SMAD3gene and rs10811661SNP loci of CDKN2A/B gene are all associated with diabetic nephropathy, especially rs1526167SNP (P=0.001887).2.Nine genes and16SNPs measured in this study have no significant interaction with diabetic nephropathy.Conclusion:We found novel associations between gene variants in TOX CDKN2A/B and SMAD3loci and diabetic nephropathy. Whether diabetes mellitus developed to diabetic nephropathy may be related with gene variants of TOX,CDKN2A/B and SMAD3loci. These results we found require further replication in order to confirm their role in diabetic nephropathy susceptibility and clarify their role in other microvascular disease.