Adiponectin (+276 G/T), Tumor Necrosis Factor-alpha (-308 G/A) and Interleukin-6 (-174 C/G) Genes Polymorphisms in Egyptian Type 2 Diabetic Patients

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines. Adiponectin, tumor necrosis factor-α (TNF-α), interleukin-6 (Il-6), are important cytokines mediators in the pathogenesis of T2DM. The single nucleotide polymorphisms (SNPs) present in the regulatory regions of cytokine genes often have an impact on their expression levels.Aim: Explore potential associations between SNP+276 G/T of adiponectin, SNP -308 G/A of TNF-α and SNP -174 C/G of IL-6 genes with T2DM and to assess its influence on their serum levels. Subjects and Methods:From the Egyptian population, we enrolled 95 T2DM patients and 85 non-diabetic controls. Serum adiponectin, TNF-α and IL-6 were measured. Genotyping for three SNPs of the adiponectin, TNF-α and IL-6 genes was performed by polymerase chain reaction-restriction fragment length polymorphism.Results: Subjects with the GT/TT genotype of SNP 276 were at increased risk for T2DM (OR=15.88, CI=7.56-33.31, P ≤ 0.01) and associated with hypoadiponectinemia compared with the GG genotype. Furthermore, the allelic frequency of the A allele of SNP 308 was significantly different between T2DM patients compared to controls (X 2 =30.54, P ≤ 0.0001). Moreover, Individuals with T2DM carrying the GA/AA genotypes had significantly higher serum TNF-α levels than those carrying GG genotype. In addition, Carriers of G allele of IL-6 were significantly more likely associated with T2DM.

Impact of inflammatory cytokine and adipokine gene variations in the development of HIV‐associated lipodystrophy

“…In addition, in Korean and Indian patients, the APM1 − 11377C/G polymorphism was associated with low circulating adiponectin levels 81 . In Caucasian HIV‐1‐infected patients, the ADIPOQ + 276G/T genotype was associated with an increased risk of developing high triglyceride levels 82 and increased the risk of occurrence of type 2 diabetes mellitus (T2DM) 83 . Individuals with the +45G major allele of adiponectin were at greater risk of T2DM, but there was no association between single‐nucleotide polymorphism (SNP) +45 and serum adiponectin level 84 .…”

“…81 In Caucasian HIV-1-infected patients, the ADIPOQ + 276G/T genotype was associated with an increased risk of developing high triglyceride levels 82 and increased the risk of occurrence of type 2 diabetes mellitus (T2DM). 83 Individuals with the +45G major allele of adiponectin were at greater risk of T2DM, but there was no association between single-nucleotide polymorphism (SNP) +45 and serum adiponectin level. 84 In HIVinfected individuals on HAART, the APM À 11377C/G polymorphism was associated with higher adiponectin levels.…”