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

Coron Artery Dis. 2005 Dec;16(8):489-93. doi: 10.1097/00019501-200512000-00006.

Abstract

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-alpha. The expression of this cytokine is modulated by a polymorphism located at nucleotide -308 of tumor necrosis factor-alpha promoter gene. The objective of our study is to verify whether tumor necrosis factor-alpha -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-alpha -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-alpha -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-alpha -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-alpha -308 polymorphism and the occurrence of STEMI, and suggests that the tumor necrosis factor-alpha -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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Creatine Kinase, MB Form / blood
  • Electrocardiography*
  • Female
  • Humans
  • L-Lactate Dehydrogenase / blood
  • Male
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / physiopathology
  • Myocardial Ischemia / genetics*
  • Myocardial Ischemia / physiopathology
  • Myoglobin / blood
  • Polymorphism, Genetic*
  • Risk Factors
  • Troponin I / blood
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Biomarkers
  • Myoglobin
  • TNF protein, human
  • Troponin I
  • Tumor Necrosis Factor-alpha
  • L-Lactate Dehydrogenase
  • Creatine Kinase, MB Form