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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Krayenbuehl
P-A
PA
Department of Internal Medicine, Medical Policlinic, University Hospital of Zurich, Zurich, Switzerland.
Wiesli
P
P
Schmid
M
M
Schmid
C
C
Ehses
J A
JA
Hersberger
M
M
Vetter
W
W
Schulthess
G
G
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D016207:Cytokines / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D001241:Aspirin