Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory markers in patients with type 2 diabetes and peripheral arterial disease

Aims: To determine whether the G(-174)C interleukin 6 (IL-6) polymorphism influences the development of peripheral arterial disease (PAD) in individuals with type 2 diabetes. This was investigated by comparing the distribution of G(-174)C genotypes between patients with type 2 diabetes and PAD (PAD ⁺) and those with type 2 diabetes but without PAD (PAD^-). Plasma concentrations of IL-6, fibrinogen, C reactive protein (CRP), and vascular endothelial growth factor (VEGF) were also compared in PAD⁺ and PAD^- patients. Methods: Blood samples were collected from 146 PAD⁺ and 144 PAD^- patients. SfaNI was used to determine the G(-174)C genotype. Plasma concentrations of IL-6, fibrinogen, CRP, and VEGF were measured by an enzyme linked immunosorbent assay. Results: The GG genotype was more common in PAD⁺ patients than in PAD^- patients. PAD⁺ patients also had increased mean plasma concentrations of IL-6, fibrinogen, CRP, and VEGF compared with PAD^- patients. Mean plasma concentrations of IL-6, fibrinogen, and CRP in both PAD⁺ and PAD ^- patients were higher in those with the GG genotype than in those with the GC or CC genotypes. In contrast, mean plasma concentrations of VEGF in PAD⁺ and PAD patients were not significantly different between those with different G(-174)C genotypes. Conclusions: These results support a model in which the GG genotype promotes PAD development among individuals with type 2 diabetes by inducing increased release of IL-6. Higher concentrations of IL-6 among those with the GG genotype is associated with increased plasma concentrations of fibrinogen and CRP.