TNF-alpha -308G>A Polymorphism Modulates Cytokine Serum Concentrations and Macrovascular Complications in Diabetic Patients on Aspirin

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.

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

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