Tumor necrosis factor-alpha gene -308G>A polymorphism is associated with ST-elevation myocardial infarction and with high plasma levels of biochemical ischemia markers

OBJECTIVES: As is well known, acute myocardial infarction presents two electrocardiogram (EKG) patterns, ST-elevation (STEMI) and no ST-elevation (NSTEMI), characterized by different coronary artery thrombotic occlusion. Growing evidence shows that inflammation plays a central role in the pathogenesis of acute myocardial infarction. Among the factors that promote inflammation and arterial thrombosis, one of the most important is the proinflammatory cytokine tumor necrosis factor-α. The expression of this cytokine is modulated by a polymorphism located at nucleotide -308 of tumor necrosis factor-α promoter gene. The objective of our study is to verify whether tumor necrosis factor-α -308 polymorphism is associated with risk of acute myocardial infarction (STEMI and NSTEMI) or with biochemical myocardial ischemia markers, such as troponin I, creatine kinase-MB, lactate dehydrogenase and myoglobin. METHODS: We analyzed tumor necrosis factor-α -308 polymorphism in a total of 603 study participants: 293 elderly patients affected by acute myocardial infarction (STEMI and NSTEMI) and 310 healthy controls. RESULTS: We found that individuals carrying the tumor necrosis factor-α -308 AG+AA genotypes are significantly more represented among acute myocardial infarction patients affected by STEMI than among NSTEMI patients (OR=1.86, 95% CI 1.08-3.21, p=0.027) and healthy controls (OR=1.64, 95% CI 1.03-2.64, p=0.046). Furthermore, the patients carrying tumor necrosis factor-α -308 AG+AA genotypes displayed significant increased levels of biochemical myocardial ischemia markers. CONCLUSIONS: Our study shows a significant association between the tumor necrosis factor-α -308 polymorphism and the occurrence of STEMI, and suggests that the tumor necrosis factor-α -308 polymorphism could play a role in the pathogenesis of cardiac ischemic damage, AA+AG genotype carrier individuals being likely to be affected by more severe ischemic damage than the rest of the population.