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

In Brief 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. Acute myocardial infarction presents two EKG patterns, ST-elevation (STEMI) and no ST-elevation (NSTEMI), characterized by different coronary artery thrombotic occlusion. Growing evidence suggests that inflammation plays a central role in the pathogenesis of acute myocardial infarction. Tumor necrosis factor-α is one of the most important proinflammatory cytokines and its genetic expression ismodulated by a polymorphismlocated at nucleotide −308. Weanalyzed the tumor necrosis factor-α −308 polymorphism in atotal of 603 study participants (293 elderly patients with acute myocardial infarction and 310 healthy controls). We found that individuals carrying 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) andhealthy controls (OR=1.64, 95%CI1.03–2.64, P=0.046) anddisplayed significant increased levels of biochemicalmyocardial ischemia markers. Our study suggests that tumornecrosis factor-α −308 polymorphism could play a role in thepathogenesis of cardiac ischemic damage.