Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory markers in patients with type 2 diabetes and peripheral arterial disease.
OBJECTIVE
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.
Libra
M
M
Department of Biomedical Sciences, University of Catania, Via Androne, 83-95124, Catania, Italy.
Signorelli
S S
SS
Bevelacqua
Y
Y
Navolanic
P M
PM
Bevelacqua
V
V
Polesel
J
J
Talamini
R
R
Stivala
F
F
Mazzarino
M C
MC
Malaponte
G
G
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000097:blood / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D005340:Fibrinogen; D002097:C-Reactive Protein