title: Association of tumor necrosis factor (TNF) promoter polymorphisms with plasma TNF-α levels and susceptibility to diabetic nephropathy in North Indian population.
abstract: OBJECTIVE
  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-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.
  
  
  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-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.
  
  
  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-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.
authors.affiliation: Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India.
authors.forename: Stuti
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Mehndiratta
authors.affiliation: Department of Medicine, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India.
authors.forename: Sarathi
authors.initials: S
authors.lastname: Kalra
authors.affiliation: Department of Medicine, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India.
authors.forename: Om P
authors.initials: OP
authors.lastname: Kalra
authors.affiliation: Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India.
authors.forename: Rimi
authors.initials: R
authors.lastname: Shukla
authors.affiliation: Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. Electronic address: jassigambhir@yahoo.co.in.
authors.forename: Jasvinder K
authors.initials: JK
authors.lastname: Gambhir
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics*
chemical_list: C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Diabetic nephropathy; TNF-alpha levels; Type 2 diabetes mellitus; −1031T/C polymorphism; −863C/A polymorphism