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

Figure 1 NFKB1 gene and inflammatory markers: Probable mechanisms in the pathogenesis of diabetic nephropathy. Hypoglycemia induced ROS and TNF-α leads to activation of IKK. IKK causes phosphorylation of IκBα bound to p50/p65. Phosphorylated IκBα dissociate from p50/p65 leading to nuclear translocation of unbound heterodimer p50/p65 (NF-κB). Binding of NF-κB to promoter gene causes translation of p65. Ins allele, rs28362491 NFKB1 gene, if present, causes increase expression of p50. Hence there is increased production of p50/p65 heterodimer complex. This heterodimer acts on its downstream proinflammatory targets viz: MCP-1 and TNF-α leading to its synthesis. MCP-1 is a positive regulator of TNF-α and vice versa. Both MCP-1 and TNF-α causes renal damage leading to development of Diabetic nephropathy. ROS: Reactive oxygen species; TNF-α: Tumor necrosis factor-alpha; IKK: IκB kinase complex; MCP-1: Monocyte chemoattractant protein-1.