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Genetic impact of TNF-beta on risk factors for coronary atherosclerosis.

BACKGROUND
Inflammatory processes are considered to play an important role in the development of coronary atherosclerosis. The proinflammatory cytokine, tumor necrosis factor beta (TNF-beta), is thought to contribute to the pathogenesis of atherosclerosis.


STUDY DESIGN
In this clinical study, the influence of genetic variants of TNF-beta (c.7G>A, IVS1+90G>A, C13R, T60N) on major coronary risk factors, including gender, smoking, history of cardiovascular diseases, biochemical data (inflammatory markers, factors of lipid metabolism, coagulation/fibrinolysis balance), and angiographically-proven coronary state, was investigated in 176 European Caucasian probands (130 males, mean age: 51.9 +/- 8.9 y).


RESULTS
The most frequent combinations of the polymorphisms investigated were significantly associated with four of the coronary risk factors evaluated: hypertension, body mass index, the common inflammatory marker TNF-alpha (mRNA expression), and fibrinogen (p < 0.05). However, on testing the impact of the genetic background on the incidence of coronary stenosis in this sample of European Caucasians, no significant influence of these polymorphisms (stepwise binary logistic regression analysis) could be proven. These findings emphasise a distinct influence of TNF-beta polymorphisms on important modulators of the development of coronary atherosclerosis, but exclude its genetic background, investigated in this study as an independent coronary risk factor.