Increased levels of circulating (TNF-α) is associated with (-308G/A) promoter polymorphism of TNF-α gene in Diabetic Nephropathy

The crucial role of Tumor Necrosis Factor-alpha (TNF-alpha) on renal function in patients with Diabetic Nephropathy (DN) has been well documented. The present study was designed to investigate the association of TNF-alpha [-308G/A, (rs1800629)] single nucleotide polymorphism (SNP) on the susceptibility to DN subjects and to correlate it with the plasma levels of TNF-alpha along with circulatory TNF-alpha receptor super family cytokines (sTNFR-1 and sTNFR-2). A total of 756 subjects, were recruited and divided into groups [Group-I, Control (n = 218), Group-II, Normoalbuminuria (n=196), Group-IIIa, Microalbuminuria (n=178), Group-IIIb, Macroalbuminuria (n=164)] and were genotyped by PCR-restriction fragment length polymorphism (RFLP). Circulatory levels of TNF-alpha and sTNFR-1 & sTNFR-2 were measured using multiplex bead based assay. The 'A' allele of TNF-alpha (-308 G/A) SNP was associated with a significant risk for macroalbuminuria subjects (OR: 2.1; 95% CI: 0.8-3.7; P<0.001). A marked stepwise increase was observed in the levels of circulatory biomarkers such as TNF-alpha, sTNF-R1 and sTNF-R2 from normo to macroalbuminuria subjects. In DN subjects, the TNF-alpha level was higher in individuals who had mutant AA, than the wild GG genotype of TNF-ce gene. Our results conclude that rs1800629 polymorphism in TNF-alpha gene is associated with renal complications in T2DM subjects. (C) 2017 Elsevier B.V. All rights reserved.