Antonicelli Roberto, Olivieri Fabiola, Bonafè Massimiliano, Cavallone Luca, Spazzafumo Liana, Marchegiani Francesca, Cardelli Maurizio, Recanatini Andrea, Testarmata Paolo, Boemi Massimo, Parati Gianfranco, Franceschi Claudio
Department of Cardiology, Center of Molecular Biology, Center of Statistics and Diabetologic Unit, Italian National Research Centers on Aging (INRCA), Via della Montagnola, 81, 60121 Ancona, Italy.
Int J Cardiol. 2005 Sep 1;103(3):266-71. doi: 10.1016/j.ijcard.2004.08.064.
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are key mediators of inflammation and their increased plasma levels are associated with acute coronary syndrome (ACS). Polymorphisms in the promoter region of IL-6 (-174 G>C) and TNF-alpha (-308 G>A) demonstrated to affect gene expression were analyzed to test their predictive power for cardiovascular death over one year follow-up in elderly male ACS patients.
We assessed the IL-6 -174 G>C polymorphism and TNF-alpha -308 G>A polymorphism in 139 consecutive elderly male patients affected by an ACS, such as ST-Elevation (STEMI), No ST-Elevation (NSTEMI) Myocardial Infarction and Unstable Angina. The presence of well known risk factors for Coronary Heart Diseases (CHD) were also assessed in all ACS patients. Survival rate was assessed after one year follow-up.
We found that IL-6 -174 G>C polymorphism is an independent predictor of cardiovascular death after an ACS in male patients. In particular ACS patients carrying the IL-6 -174 C- (GG) genotypes showed a marked increase in one year follow-up mortality rate (HR=3.89, 95% CI 1.71-8.86, p=0.001). Moreover CRP serum levels > or = 5.5 mg/dl (HR= 3.79, 95% CI 1.71-8.42, p=0.001), a history of CHD (HR=2.96, 95% CI 1.22-7.20, p=0.016) and the absence of statins treatment (HR=3.27, 95% CI 1.17-9.18, p=0.021), significantly increased one year risk of death in male ACS patients.
These data suggest that IL-6 -174 G>C polymorphism can be added to other clinical markers in order to identify a subgroup of elderly ACS male patients at higher risk of death.
白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）是炎症的关键介质，其血浆水平升高与急性冠状动脉综合征（ACS）相关。分析了IL-6（-174 G>C）和TNF-α（-308 G>A）启动子区域中已证实会影响基因表达的多态性，以测试其对老年男性ACS患者一年随访期内心血管死亡的预测能力。
我们评估了139例连续的老年男性ACS患者（如ST段抬高型心肌梗死（STEMI）、非ST段抬高型心肌梗死（NSTEMI）和不稳定型心绞痛）的IL-6 -174 G>C多态性和TNF-α -308 G>A多态性。还评估了所有ACS患者中已知的冠心病（CHD）危险因素。随访一年后评估生存率。
我们发现IL-6 -174 G>C多态性是男性患者ACS后心血管死亡的独立预测因素。特别是携带IL-6 -174 C-（GG）基因型的ACS患者在一年随访期内死亡率显著增加（HR=3.89，95%CI 1.71-8.86，p=0.001）。此外，血清CRP水平≥5.5 mg/dl（HR=3.79，95%CI 1.71-8.42，p=0.001）、有CHD病史（HR=2.96，95%CI 1.22-7.20，p=0.016）以及未接受他汀类药物治疗（HR=3.27，95%CI 1.17-9.18，p=0.021），均显著增加男性ACS患者一年的死亡风险。
这些数据表明，IL-6 -174 G>C多态性可添加到其他临床标志物中，以识别死亡风险较高的老年ACS男性患者亚组。
