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Int J Biol Macromol. 2018 Feb;107(Pt B):2113-2121. doi: 10.1016/j.ijbiomac.2017.10.078. Epub 2017 Oct 16.

Increased levels of circulating (TNF-α) is associated with (-308G/A) promoter polymorphism of TNF-α gene in Diabetic Nephropathy.

Author information

1
Life Science Division, SRM Research Institute, SRM University, Kattankulathur 603 203, Tamilnadu, India.
2
Department of Biochemistry and Molecular Genetics, Prof. M. Viswanathan Diabetes Research Centre and M.V. Hospital for Diabetes (A WHO Collaborating Centre for Research, Education & Training in Diabetes), Royapuram, Chennai 600 013, Tamilnadu, India.
3
Department of Biotechnology, School of Bio-Engineering, SRM University, Kattankulathur 603 203, Tamilnadu, India.
4
Department of Biochemistry and Molecular Genetics, Prof. M. Viswanathan Diabetes Research Centre and M.V. Hospital for Diabetes (A WHO Collaborating Centre for Research, Education & Training in Diabetes), Royapuram, Chennai 600 013, Tamilnadu, India. Electronic address: drvijay@mvdiabetes.com.
5
Life Science Division, SRM Research Institute, SRM University, Kattankulathur 603 203, Tamilnadu, India. Electronic address: ramkumar.km@res.srmuniv.ac.in.

Abstract

The crucial role of Tumor Necrosis Factor-α (TNF-α) on renal function in patients with Diabetic Nephropathy (DN) has been well documented. The present study was designed to investigate the association of TNF-α [-308G/A, (rs1800629)] single nucleotide polymorphism (SNP) on the susceptibility to DN subjects and to correlate it with the plasma levels of TNF-α along with circulatory TNF-α receptor super family cytokines (sTNFR-1 and sTNFR-2). A total of 756 subjects, were recruited and divided into groups [Group-I, Control (n=218), Group-II, Normoalbuminuria (n=196), Group-IIIa, Microalbuminuria (n=178), Group-IIIb, Macroalbuminuria (n=164)] and were genotyped by PCR-restriction fragment length polymorphism (RFLP). Circulatory levels of TNF-α and sTNFR-1 & sTNFR-2 were measured using multiplex bead based assay. The 'A' allele of TNF-α (-308 G/A) SNP was associated with a significant risk for macroalbuminuria subjects (OR: 2.1; 95% CI: 0.8-3.7; P<0.001). A marked stepwise increase was observed in the levels of circulatory biomarkers such as TNF-α, sTNF-R1 and sTNF-R2 from normo to macroalbuminuria subjects. In DN subjects, the TNF-α level was higher in individuals who had mutant AA, than the wild GG genotype of TNF-α gene. Our results conclude that rs1800629 polymorphism in TNF-α gene is associated with renal complications in T2DM subjects.

KEYWORDS:

Diabetic Nephropathy; Macroalbuminuria; Microalbuminuria; Normoalbuminuria; Single nucleotide polymorphism; Tumor necrosis factor-α

PMID:
29042282
DOI:
10.1016/j.ijbiomac.2017.10.078
[Indexed for MEDLINE]

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