肿瘤坏死因子-α基因-308G>A多态性与ST段抬高型心肌梗死以及血浆中高水平的生化缺血标志物相关。

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

作者信息

Antonicelli Roberto, Olivieri Fabiola, Cavallone Luca, Spazzafumo Liana, Bonafè Massimiliano, Marchegiani Francesca, Cardelli Maurizio, Galeazzi Roberta, Giovagnetti Simona, Perna Gian Piero, Franceschi Claudio

机构信息

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.

出版信息

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

DOI:10.1097/00019501-200512000-00006

PMID:16319659

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.

摘要

目的

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。

方法

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。

结果

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。