ORIGINAL ARTICLE

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

M Libra¹, S S Signorelli², Y Bevelacqua¹, P M Navolanic¹, V Bevelacqua¹, J Polesel³, R Talamini³, F Stivala¹, M C Mazzarino¹ and G Malaponte¹

¹ Department of Biomedical Sciences, University of Catania, Via Androne, 83-95124, Catania, Italy
² Department of Internal Medicine, Angiology Unit, University of Catania
³ Epidemiology Unit, Centro di Riferimento Oncologico, 33081 Aviano, Italy

Correspondence to:
Correspondence to:
Dr G Malaponte
Department of Biomedical Sciences, University of Catania, Via Androne, 83-95124 Catania, Italy; g.malaponte{at}unict.it

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.

Abbreviations: CRP, C reactive protein; IL-6, interleukin 6; PAD, peripheral arterial disease; PCR, polymerase chain reaction; VEGF, vascular endothelial growth factor

Keywords: inflammation; interleukin-6; peripheral arterial disease; type 2 diabetes mellitus

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