Association of NFKB1 gene polymorphism (rs28362491) with levels of inflammatory biomarkers and susceptibility to diabetic nephropathy in Asian Indians.

AIM: To investigate the association of NFKB1 gene -94 ATTG insertion/deletion (rs28362491) polymorphism with inflammatory markers and risk of diabetic nephropathy in Asian Indians. METHODS: A total of 300 subjects were recruited (100 each), normoglycemic, (NG); type 2 diabetes mellitus (T2DM) without any complications (DM) and T2DM with diabetic nephropathy [DM-chronic renal disease (CRD)]. Analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism and ELISA. Pearson's correlation, analysis of variance and logistic regression were used for statistical analysis. RESULTS: The allelic frequencies of -94 ATTG insertion/deletion were 0.655/0.345 (NG), 0.62/0.38 (DM) and 0.775/0.225 (DM-CRD). The -94 ATTG ins allele was associated with significantly increased levels of urinary monocyte chemoattractant protein-1 (uMCP-1); uMCP-1 (P = 0.026) and plasma tumor necrosis factor-alpha (TNF-α); TNF-α (P = 0.030) and almost doubled the risk of diabetic nephropathy (OR = 1.91, 95%CI: 1.080-3.386, P = 0.025). CONCLUSION: -94 ATTG ins/ins polymorphism might be associated with increased risk of developing nephropathy in Asian Indian subjects with diabetes mellitus.

Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population.

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide. It results from diverse etiologies, diabetes being a frontrunner amongst them. Type 2 diabetes mellitus (DM) is being increasingly recognized as a proinflammatory state with increased oxidative stress which enormously increases the risk of micro and macro vascular diseases. This study was planned to explore the possible association between tumor necrosis factor-alpha (TNF-α), urinary monocyte chemoattractant protein-1 (uMCP-1), high-sensitivity C-reactive protein (hsCRP) and parameters of oxidative stress in patients with Type 2 diabetes mellitus (DM) and diabetic chronic kidney disease (DM-CKD). Fifty patients each were recruited in DM, DM-CKD and healthy control groups. Plasma TNF-α, hsCRP and uMCP-1 levels as inflammatory mediators were measured by ELISA, reduced glutathione (GSH), ferric reducing ability of plasma (FRAP) as parameters of antioxidant activity and malondialdehyde (MDA) as marker of oxidative stress, were measured spectrophotometrically. Plasma TNF-α, hsCRP and uMCP-1 were significantly higher in DM-CKD compared to DM and healthy controls. Lipid peroxidation, measured as MDA was significantly higher in patients with DM-CKD as compared to patients with DM and healthy controls. Further, antioxidant capacity of blood measured as FRAP and GSH was found to be significantly lower in patients with DM and DM-CKD as compared to healthy controls (p<0.001). Plasma TNF-α and uMCP-1 showed a significant positive correlation with HbA1c (r=0.441, 0.643), hsCRP (r=0.400, 0.584) and MDA (r=0.423, 0.759) and significant negative correlation with GSH (R=-0.370, -0.800) and FRAP (r=-0.344, -0.684) Increased inflammatory markers viz. TNF-α, hsCRP and uMCP-1 and markers of oxidative stress i.e. increased MDA and decreased GSH and FRAP in DM-CKD suggest an important role of inflammation and oxidative stress in the pathogenesis of renal damage in diabetic patients.