title: Genetic association of IL-6, TNF-α and SDF-1 polymorphisms with serum cytokine levels in diabetic foot ulcer.
abstract: The IL-6 -174G/C (rs1800795), TNF-α -308G/A (rs1800629) and -238G/A (rs361525) and SDF-1 801G/A (rs1801157) are well characterized SNPs which have previously been linked to various diabetic complications. However, the involvement of these SNPs in DFU remains poorly studied. In the present study we looked at the association of these SNPs with DFU (disease phenotype) and correlated it with the serum levels of cytokines (intermediate phenotype) along with other clinical risk factors of DFU (adiponectin, leptin and hsCRP). Genotyping was carried out in Normal glucose tolerance ((NGT)/Control=106), T2DM without DFU (T2DM=139), T2DM with neuropathy (DFU-DN=191) and T2DM with PVD (DFU-PVD=79) subjects by PCR-RFLP and the serum cytokine levels were determined by ELISA. IL-6 -176 "C" allele conferred significant protection against T2DM but not against DFU. TNF-α -308 "A" allele (but not -238 SNP) conferred significant susceptibility towards both T2DM and DFU-DN. The SDF-1 "A" allele conferred significant protection against both DM and DFU-DN but not against DFU-PVD. Further, these alleles were shown to influence the serum cytokine/chemokine levels under diabetic conditions. Thus SNPs in cytokine/chemokine genes serve as valuable biomarkers for DFU.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Prof M.Viswanathan Diabetes Research Centre, Chennai, India.
authors.forename: Umapathy
authors.initials: U
authors.lastname: Dhamodharan
authors.affiliation: Department of Biochemistry and Molecular Genetics, Prof M.Viswanathan Diabetes Research Centre, Chennai, India. Electronic address: drvijay@mvdiabetes.com.
authors.forename: Vijay
authors.initials: V
authors.lastname: Viswanathan
authors.affiliation: Department of Biochemistry and Molecular Genetics, Prof M.Viswanathan Diabetes Research Centre, Chennai, India.
authors.forename: Ezhilarasi
authors.initials: E
authors.lastname: Krishnamoorthy
authors.affiliation: Department of Biochemistry, Central Leather Research Institute, Chennai, India.
authors.forename: Rama
authors.initials: R
authors.lastname: Rajaram
authors.affiliation: Department of Genetics, Dr.A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, India. Electronic address: cvaravindhan@gmail.com.
authors.forename: Vivekanandhan
authors.initials: V
authors.lastname: Aravindhan
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000097:blood / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics; D017719:Diabetic Foot / Q000097:blood* / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C508600:IL6 protein, human; D015850:Interleukin-6; D020738:Leptin; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Diabetic foot ulcer; HOMA-IR; IL-6; Polymorphisms; SDF-1; TNF-α; hsCRP