PMID- 25704106 OWN - NLM STAT- MEDLINE DCOM- 20160216 LR - 20150321 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 29 IP - 3 DP - 2015 Apr TI - Association of tumor necrosis factor (TNF) promoter polymorphisms with plasma TNF-alpha levels and susceptibility to diabetic nephropathy in North Indian population. PG - 338-42 LID - S1056-8727(15)00003-3 [pii] LID - 10.1016/j.jdiacomp.2015.01.002 [doi] AB - 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-alpha 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% 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-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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Gupta, Stuti AU - Gupta S AD - Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. FAU - Mehndiratta, Mohit AU - Mehndiratta M AD - Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. FAU - Kalra, Sarathi AU - Kalra S AD - Department of Medicine, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. FAU - Kalra, Om P AU - Kalra OP AD - Department of Medicine, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. FAU - Shukla, Rimi AU - Shukla R AD - Molecular Diagnostic Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. FAU - Gambhir, Jasvinder K AU - Gambhir JK AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150109 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (TNF protein, human) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Alleles MH - Case-Control Studies MH - Diabetes Mellitus, Type 2/complications/epidemiology/*genetics MH - Diabetic Nephropathies/epidemiology/*genetics MH - Female MH - Gene Frequency MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - India/epidemiology MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - *Promoter Regions, Genetic MH - Tumor Necrosis Factor-alpha/*blood/*genetics OTO - NOTNLM OT - Diabetic nephropathy OT - TNF-alpha levels OT - Type 2 diabetes mellitus OT - -1031T/C polymorphism OT - -863C/A polymorphism EDAT- 2015/02/24 06:00 MHDA- 2016/02/18 06:00 CRDT- 2015/02/24 06:00 PHST- 2014/09/17 00:00 [received] PHST- 2014/12/09 00:00 [revised] PHST- 2015/01/05 00:00 [accepted] PHST- 2015/02/24 06:00 [entrez] PHST- 2015/02/24 06:00 [pubmed] PHST- 2016/02/18 06:00 [medline] AID - S1056-8727(15)00003-3 [pii] AID - 10.1016/j.jdiacomp.2015.01.002 [doi] PST - ppublish SO - J Diabetes Complications. 2015 Apr;29(3):338-42. doi: 10.1016/j.jdiacomp.2015.01.002. Epub 2015 Jan 9.