TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin

• Published in: Experimental and clinical endocrinology & diabetes Vol. 115; no. 5; p. 322
• Main Authors: Krayenbuehl, P-A, Wiesli, P, Schmid, M, Schmid, C, Ehses, J A, Hersberger, M, Vetter, W, Schulthess, G
• Format: Journal Article
• Language: English
• Published: Germany 01-05-2007
• Subjects: Aged; Aspirin - therapeutic use; Cerebrovascular Disorders - epidemiology; Cerebrovascular Disorders - etiology; Cerebrovascular Disorders - genetics; Coronary Disease - epidemiology; Coronary Disease - etiology; Coronary Disease - genetics; Cytokines - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetic Angiopathies - epidemiology; Diabetic Angiopathies - genetics; Diabetic Angiopathies - prevention & control; Female; Gene Frequency; Heterozygote; Humans; Male; Middle Aged; Peripheral Vascular Diseases - epidemiology; Peripheral Vascular Diseases - etiology; Peripheral Vascular Diseases - genetics; Polymorphism, Single Nucleotide; Prevalence; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0947-7349
• DOI: 10.1055/s-2007-960493

Tumor necrosis factor (TNF)-alpha 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-alpha -308G>A polymorphism and coronary artery disease.
Vascular complications and cytokine serum concentrations were assessed as a function of the TNF-alpha -308G>A polymorphism in 76 diabetic patients on low-dose aspirin.
Of 76 adult diabetic patients, 18 (24%) carried the TNF-alpha -308A allele (17 AG, 1 AA) and 58 (76%) carried wild-type alleles (GG). Prevalence of macrovascular complications was 33% in TNF-alpha -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-alpha -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-beta (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-alpha -308G>A polymorphism (p<0.001) and serum concentrations of HDL-cholesterol (p=0.007) while confounding effects of further variables were excluded.
TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin. Diabetic carriers of the TNF-alpha -308A allele might benefit more from a prophylaxis with low dose aspirin than non-carriers.