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

Abstract

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.