The -308 G/A tumor necrosis factor-alpha gene dimorphism: a risk factor for unstable angina.

Since the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) may play a major role in the pathophysiology of acute coronary syndromes, 299 consecutive male patients hospitalized for coronary artery disease (i.e., lumen lost > or = 50%) were genotyped for the functional -308G/A TNF-alpha polymorphism using restriction fragment length polymorphism method, in order to evaluate its potential association with the risk of unstable angina and/or myocardial infarction. A higher frequency of carriers of the A allele was observed in patients with unstable angina (n = 58) when compared to control patients with stable angina (n = 95) (39.66% vs. 23.16% respectively, p = 0.029, odds ratio = 2.2) but not in patients with myocardial infarction (n = 146) (23.97% vs. 23.16%, p = NS). Furthermore, we evidenced an interaction of the polymorphism studied with body mass index in patients with unstable angina. Thus, when stratified analysis was performed, results in patients with a body mass index < or = 27 showed a more striking association between A allele carriage frequency and unstable angina (p = 0.012, odds ratio = 3.0). These results suggest the crucial role of TNF-alpha in the mechanisms responsible for unstable angina in accordance with the concept of vulnerable plaque. On the other hand, mechanisms controlling myocardial infarction appear more complex and heterogeneous.