Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway ; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway.
PLoS One. 2013 Sep 5;8(9):e74498. doi: 10.1371/journal.pone.0074498. eCollection 2013.
Interleukin (IL)-18 has been associated with severity of atherosclerosis and discussed to predict cardiovascular (CV) events. We have previously shown that the IL-18+183 G-allele significantly reduces IL-18 levels. This study was aimed to investigate the prognostic significance of the IL-18+183 A/G polymorphism (rs5744292), single and in coexistence with the matrix metalloproteinase (MMP)-9 -1562 C/T (rs3918242) polymorphism, in patients with stable coronary artery disease (CAD). Serum levels of IL-18, MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were additionally assessed.
1001 patients with angiographically verified CAD were genotyped and the biomarkers were measured accordingly. After two years follow-up, 10.6% experienced new clinical events; acute myocardial infarction (AMI), stroke, unstable angina pectoris and death.
The IL-18+183 G-allele associated with 35% risk reduction in composite endpoints after adjusting for potential covariates (p = 0.044). The IL-18+183 AA/MMP-9 -1562 CT/TT combined genotypes associated with a significant increase in risk of composite endpoints (OR = 1.87; 95% CI = 1.13-3.11, p = 0.015, adjusted). Patients with clinical events presented with significantly higher IL-18 levels as compared to patients without (p = 0.011, adjusted). The upper tertile of IL-18 levels associated with an increase in risk of AMI as compared to lower tertiles (OR = 2.36; 95% CI = 1.20-4.64, p = 0.013, adjusted).
The IL-18+183 A/G polymorphism, single and in combination with MMP-9 genotypes, may influence the risk of clinical events in stable CAD patients.
白细胞介素（IL）-18 与动脉粥样硬化的严重程度有关，并被认为可预测心血管（CV）事件。我们之前已经表明，IL-18+183 G-等位基因可显著降低 IL-18 水平。本研究旨在探讨白细胞介素（IL）-18+183A/G 多态性（rs5744292）、单态性以及与基质金属蛋白酶（MMP）-9-1562C/T（rs3918242）多态性共存时在稳定型冠状动脉疾病（CAD）患者中的预后意义。此外，还评估了血清中 IL-18、MMP-9 和基质金属蛋白酶组织抑制剂（TIMP）-1 的水平。
对 1001 例经血管造影证实的 CAD 患者进行基因分型，并相应测量生物标志物。经过两年的随访，10.6%的患者发生新的临床事件，包括急性心肌梗死（AMI）、中风、不稳定型心绞痛和死亡。
在调整潜在混杂因素后，IL-18+183 G-等位基因与复合终点的 35%风险降低相关（p = 0.044）。IL-18+183 AA/MMP-9-1562 CT/TT 联合基因型与复合终点的风险显著增加相关（OR = 1.87；95%CI = 1.13-3.11，p = 0.015，调整）。与无临床事件的患者相比，发生临床事件的患者血清 IL-18 水平显著升高（p = 0.011，调整）。与下两个三分位相比，IL-18 水平的上三分位与 AMI 风险增加相关（OR = 2.36；95%CI = 1.20-4.64，p = 0.013，调整）。
IL-18+183 A/G 多态性、单态性以及与 MMP-9 基因型的结合可能影响稳定型 CAD 患者的临床事件风险。
