Montali Anna, Barillà Francesco, Tanzilli Gaetano, Vestri Annarita, Fraioli Antonio, Gaudio Carlo, Martino Francesco, Mezzetti Andrea, Cipollone Francesco, Arca Marcello
Department of Clinical and Medical Therapy, Atherosclerosis Unit, Lipid Clinic Center of La Sapienza University of Rome, Rome, Italy.
Cardiology. 2010;115(3):236-42. doi: 10.1159/000298880. Epub 2010 Mar 19.
The -765G>C variation (rs20417 SNP) in the promoter of cyclooxygenase-2 (COX-2) gene has been demonstrated to lower COX-2 enzyme activity in the vasculature, thus affecting atherosclerotic plaque growth and stability. Therefore, this genetic variant may be a candidate influencing the residual risk.
In 285 coronary patients the incidence of major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular deaths, non-fatal myocardial infarction and stroke, unstable angina and revascularization procedures, was monitored for a median of 7.8 years. The genotypes were obtained in 231 patients (81%) by PCR amplification and FAU I digestion.
89 MACEs (38.5%) were recorded during the follow-up in genotyped patients. Their incidence was not different in patients with GC or CC when compared with those with GG genotype (46.2 vs. 35.5% respectively; p = 0.14). Kaplan-Meyer analysis did not demonstrate any influence of COX-2 genotypes on the event-free survival time (log-rank p = 0.55). After controlling for confounders, the -765G>C carrier status was not associated with significant variation in the risk of MACE or its individual components.
These results suggest that the functional G-765C variant in the COX-2 gene is not a significant predictor of the recurrence of ischemic events in coronary patients.
环氧合酶-2(COX-2)基因启动子中的-765G>C变异(rs20417单核苷酸多态性)已被证明可降低血管系统中COX-2酶的活性,从而影响动脉粥样硬化斑块的生长和稳定性。因此,这种基因变异可能是影响残余风险的一个因素。
在285例冠心病患者中,对主要不良心血管事件(MACE)的发生率进行了中位数为7.8年的监测,MACE定义为心血管死亡、非致死性心肌梗死和中风、不稳定型心绞痛以及血运重建术的综合。通过PCR扩增和FAU I酶切在231例患者(81%)中获得了基因型。
在基因分型患者的随访期间记录到89例MACE(38.5%)。与GG基因型患者相比,GC或CC基因型患者的发生率没有差异(分别为46.2%和35.5%;p = 0.14)。Kaplan-Meyer分析未显示COX-2基因型对无事件生存时间有任何影响(对数秩检验p = 0.55)。在控制混杂因素后,-765G>C携带者状态与MACE风险或其各个组成部分的显著变化无关。
这些结果表明,COX-2基因中功能性的G-765C变异不是冠心病患者缺血事件复发的重要预测指标。