Tumor necrosis factor-alpha gene -308G>A polymorphism is associated with ST-elevation myocardial infarction and with high plasma levels of biochemical ischemia markers.
OBJECTIVE
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.
Antonicelli
Roberto
R
Center of Molecular Biology, Department of Cardiology-CCU and Center of Statistics, Italian National Research Centers on Aging (I.N.R.C.A.), Ancona, Italy. r.antonicelli@inrca.it
Olivieri
Fabiola
F
Cavallone
Luca
L
Spazzafumo
Liana
L
Bonafè
Massimiliano
M
Marchegiani
Francesca
F
Cardelli
Maurizio
M
Galeazzi
Roberta
R
Giovagnetti
Simona
S
Perna
Gian Piero
GP
Franceschi
Claudio
C
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000235:genetics* / Q000503:physiopathology; D009211:Myoglobin / Q000097:blood; D011110:Polymorphism, Genetic; D012307:Risk Factors; D019210:Troponin I / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015415:Biomarkers; D009211:Myoglobin; C439524:TNF protein, human; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form