Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.
Hum Immunol. 2011 Aug;72(8):636-40. doi: 10.1016/j.humimm.2011.04.005. Epub 2011 Apr 29.
Inflammation and immune response play an important role in the pathogenesis of atherosclerosis. In this prospective study we tested the hypothesis of whether polymorphic variations in the NOD2/CARD15 gene may influence the risk of developing clinically evident coronary artery disease (CAD). ARG702TRP, GLY908ARG, and Leu1007fsinsC NOD2/CARD15 polymorphisms were analyzed in 109 consecutive patients with angiographically documented CAD and in 109 age- and sex-matched healthy controls. The ARG702TRP, GLY908ARG, and Leu1007fsinsC polymorphisms were analyzed by polymerase chain reaction followed by restriction digestion. The prevalence of the Leu1007fsinsC polymorphism was significantly increased in CAD patients compared with controls (11.9% vs 1.8%; odds ratios (OR) 7.2, 95% confidence interval (95% CI) 1.5-32.9; p = 0.01), especially in those presenting with an acute coronary syndrome (OR 5.7; 95% CI 1.1-39.7; p = 0.034 vs stable angina). In CAD patients the frequency of GLY908ARG polymorphism was significantly lower (1.8% vs 6.4% in controls; OR 0.05, 95% CI 0.01-0.69; p = 0.031, at multivariable analysis) and the prevalence of the ARG702TRP polymorphism was higher compared with controls (10.1% vs 3.7%; OR 2.9, 95% CI 0.91-9.6; p = 0.07). We report in a Caucasian population that NOD2/CARD15 polymorphisms influence the development of clinically evident and angiographically documented coronary artery disease. In particular, the Leu1007fsinsC polymorphism was associated with an increased risk of clinically evident and angiographically documented coronary atherosclerosis and clinical destabilization of coronary plaques, whereas the GLY908ARG polymorphism demonstrated a protective effect on coronary atherogenesis. These correlations were independent of cardiovascular risk factors at multivariable analysis. These findings may contribute to the identification of a novel genetic approach for the stratification of cardiovascular risk profile.
炎症和免疫反应在动脉粥样硬化的发病机制中起着重要作用。在这项前瞻性研究中，我们检验了以下假设：NOD2/CARD15 基因的多态性变异是否可能影响临床明显冠心病（CAD）的发病风险。对 109 例经血管造影证实的 CAD 连续患者和 109 例年龄和性别匹配的健康对照者进行 NOD2/CARD15 基因的 ARG702TRP、GLY908ARG 和 Leu1007fsinsC 多态性分析。采用聚合酶链反应（PCR）扩增，然后用限制性内切酶消化，分析 ARG702TRP、GLY908ARG 和 Leu1007fsinsC 多态性。CAD 患者 Leu1007fsinsC 多态性的发生率明显高于对照组（11.9%比 1.8%；比值比（OR）7.2，95%置信区间（95%CI）1.5-32.9；p = 0.01），尤其是急性冠状动脉综合征患者（OR 5.7；95%CI 1.1-39.7；p = 0.034 与稳定型心绞痛相比）。在 CAD 患者中，GLY908ARG 多态性的频率明显较低（1.8%比对照组 6.4%；OR 0.05，95%CI 0.01-0.69；p = 0.031，在多变量分析中），而 ARG702TRP 多态性的发生率高于对照组（10.1%比 3.7%；OR 2.9，95%CI 0.91-9.6；p = 0.07）。我们在高加索人群中报告称，NOD2/CARD15 多态性影响临床明显和血管造影证实的冠状动脉疾病的发展。特别是，Leu1007fsinsC 多态性与临床明显和血管造影证实的冠状动脉粥样硬化及冠状动脉斑块的临床不稳定相关，而 GLY908ARG 多态性对冠状动脉粥样硬化形成具有保护作用。这些相关性在多变量分析中独立于心血管危险因素。这些发现可能有助于确定一种新的遗传方法来分层心血管风险概况。
