Antonicelli Roberto, Olivieri Fabiola, Cavallone Luca, Spazzafumo Liana, Bonafè Massimiliano, Marchegiani Francesca, Cardelli Maurizio, Galeazzi Roberta, Giovagnetti Simona, Perna Gian Piero, Franceschi Claudio
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.
Coron Artery Dis. 2005 Dec;16(8):489-93. doi: 10.1097/00019501-200512000-00006.
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.
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.
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.
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.
众所周知，急性心肌梗死呈现两种心电图（EKG）模式，即ST段抬高型（STEMI）和非ST段抬高型（NSTEMI），其特征为不同的冠状动脉血栓性闭塞。越来越多的证据表明，炎症在急性心肌梗死的发病机制中起核心作用。在促进炎症和动脉血栓形成的因素中，最重要的因素之一是促炎细胞因子肿瘤坏死因子-α。该细胞因子的表达受肿瘤坏死因子-α启动子基因核苷酸-308处的多态性调节。我们研究的目的是验证肿瘤坏死因子-α -308多态性是否与急性心肌梗死（STEMI和NSTEMI）的风险或与生化心肌缺血标志物（如肌钙蛋白I、肌酸激酶-MB、乳酸脱氢酶和肌红蛋白）相关。
我们分析了总共603名研究参与者的肿瘤坏死因子-α -308多态性：293名患有急性心肌梗死（STEMI和NSTEMI）的老年患者和310名健康对照者。
我们发现，携带肿瘤坏死因子-α -308 AG+AA基因型的个体在STEMI急性心肌梗死患者中的比例显著高于NSTEMI患者（OR = 1.86，95% CI 1.08 - 3.21，p = 0.027）和健康对照者（OR = 1.64，95% CI 1.03 - 2.64，p = 0.046）。此外，携带肿瘤坏死因子-α -308 AG+AA基因型的患者生化心肌缺血标志物水平显著升高。
我们的研究表明肿瘤坏死因子-α -308多态性与STEMI的发生之间存在显著关联，并表明肿瘤坏死因子-α -308多态性可能在心脏缺血损伤的发病机制中起作用，AA+AG基因型携带者个体可能比其他人群更容易受到更严重的缺血损伤。
