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

作者：Gupta Stuti; Mehndiratta Mohit; Kalra Sarathi; Kalra Om P; Shukla Rimi; Gambhir Jasvinder K^*

来源：Journal of Diabetes and Its Complications, 2015, 29(3): 338-342.

DOI：10.1016/j.jdiacomp.2015.01.002

• Type 2 diabetes mellitus
• Diabetic nephropathy
• -863C/A polymorphism
• -1031T/C polymorphism
• TNF-alpha levels

Aim: The concept of diabetic nephropathy (DN) as a metabolic disease is now being replaced by chronic low-grade inflammatory disease. Tumor necrosis factor-alpha (TNF-alpha) 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-alpha levels and DN among subjects with type 2 diabetes (T2DM) in a population from North India.
Methods: Age 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-a levels were measured by ELISA. Analysis of variance and logistic regression were used to associate individual polymorphisms with plasma TNF-alpha levels and DN.
Results: The 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-alpha levels (p < 0.05). The -863C/A (OR = 0.439, 95% Cl = 0244-0.789, p = 0.006) and -1031T/C (OR = 3.0, 95% Cl = 1355-6.642, 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-alpha 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.

• 出版日期2015-4