Association of Tumor Necrosis Factor (TNF) promoter polymorphisms with plasma TNF-α levels and susceptibility to diabetic nephropathy in North Indian population

AimThe concept of diabetic nephropathy (DN) as a metabolic disease is now being replaced by chronic low-grade inflammatory disease. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine which plays an important role in the pathogenesis and clinical outcome of DN. Therefore, this work was planned to evaluate the association of − 863C/A (rs1800630) and − 1031T/C (rs1799964) polymorphisms in TNF gene with plasma TNF-α levels and DN among subjects with type 2 diabetes (T2DM) in a population from North India.MethodsAge and sex matched 100 healthy controls (HC), 100 T2DM subjects without nephropathy (DM) and 100 subjects with DN were screened for above polymorphisms using the PCR-RFLP methods. Plasma TNF-α levels were measured by ELISA. Analysis of variance and logistic regression were used to associate individual polymorphisms with plasma TNF-α levels and DN.ResultsThe allelic frequencies of − 863C/A were 0.86/0.14 in HC, 0.72/0.23 in DM and 0.84/0.16 in DN, and that of − 1031T/C were 0.89/0.11 in HC, 0.95/0.05 in DM and 0.80/0.20 in DN. The carriers of − 863A allele had significantly lower plasma TNF-α levels (p < 0.05). The − 863C/A (OR = 0.439, 95% CI = 0.244-0.789, p = 0.006) and − 1031T/C (OR = 3.0, 95% CI = 1.355-6.642, p = 0.007) were strongly associated with risk of development of DN.Conclusions− 863C/A was associated with low whereas − 1031T/C with high TNF-α levels. The, results suggest that − 863C/A polymorphism might be protective whereas − 1031T/C may be associated with increased risk for DN in subjects with T2DM from North India.