Article	Exp Clin Endocrinol Diabetes 2007; 115: 322-326 DOI: 10.1055/s-2007-960493
© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York
TNF-alpha -308G>A Polymorphism Modulates Cytokine Serum Concentrations and Macrovascular Complications in Diabetic Patients on Aspirin
P.-A. Krayenbuehl1, P. Wiesli1, M. Schmid2, C. Schmid2, J. A. Ehses2, M. Hersberger3, W. Vetter1, G. Schulthess1
1Department of Internal Medicine, Medical Policlinic, University Hospital of Zurich, Zurich, Switzerland 2Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital of Zurich, Zurich, Switzerland 3Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland

Abstract

Background: Tumor necrosis factor (TNF)-α has pleiotropic effects in cytokine-mediated inflammation underlying atherogenesis. Activation of this inflammatory process is assumed to be different in diabetic and non-diabetic individuals. Previous studies in non-diabetic subjects showed no association between TNF-α -308G>A polymorphism and coronary artery disease.

Methods: Vascular complications and cytokine serum concentrations were assessed as a function of the TNF-α -308G>A polymorphism in 76 diabetic patients on low-dose aspirin.

Results: Of 76 adult diabetic patients, 18 (24%) carried the TNF-α -308A allele (17 AG, 1 AA) and 58 (76%) carried wild-type alleles (GG). Prevalence of macrovascular complications was 33% in TNF-α -308A allele carriers (AG+AA) and 78% in wild-type allele carriers (GG) (p<0.001). In contrast, prevalence of microvascular complications was 78% and 84%, respectively, and did not significantly differ between the study groups. TNF-α -308A allele carriers (AG+AA) compared to wild-type allele carriers (GG) had significantly lower median serum concentrations of hs-C-reactive protein (1.5 vs 2.9 mg/L, p=0.030), interleukin 1-β (0.9 vs 1.2 ng/L, p=0.046), and interleukin-6 (3.6 vs 4.9 ng/L, p=0.023). In multiple regression analysis, the prevalence of macrovascular diabetic complications was significantly associated with TNF-α -308G>A polymorphism (p<0.001) and serum concentrations of HDL-cholesterol (p=0.007) while confounding effects of further variables were excluded.

Conclusion: TNF-α -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin. Diabetic carriers of the TNF-α -308A allele might benefit more from a prophylaxis with low dose aspirin than non-carriers.

Key words

Diabetes mellitus - TNF-alpha - aspirin - cardiovascular events - hs-C-reactive protein - hs-CRP