The Additive Contribution from Inflammatory Genetic Markers on the Severity of Cardiovascular Disease
The Additive Contribution from Inflammatory Genetic Markers on the Severity of Cardiovascular Disease
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DOI：
10.1111/j.1365-3083.2008.02187.x
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发表时间：
2009-01-01
影响因子：
3.7
通讯作者：
Videm, V.
中科院分区：
文献类型：
--
作者：
Berg, K. K.;Madsen, H. O.;Videm, V.
炎症在动脉粥样硬化的发展中起着关键作用。因此，炎症相关分子的遗传差异与动脉粥样硬化的易感性和严重性有关。我们假设，来自不同炎症重要基因的加性贡献将增加心血管疾病的严重程度。从230名接受选择性冠状动脉造影的成年人中收集血液样本。共有130名患者至少有一个主冠状动脉分支存在显著（> 50%）狭窄，100名患者没有。分析了髓过氧化物酶（MPO）-129G/A和-463G/A、Toll样受体4（TLR 4）Asp 299 Gly、白细胞介素6（IL 6）-174G/C、表面活性蛋白D（SFTPD）Met 11 Thr和调节正常T细胞表达和分泌（CCL 5）-403G/A等5个基因的6个多态性。IL 6多态性与血管造影显著的冠状动脉疾病显著相关（P = 0.017），在校正年龄、性别、吸烟和高胆固醇血症后，这种关系仍然存在（P = 0.007）。TLR 4（P = 0.050）和SFTPD（P = 0.058）多态性在单变量分析中也与冠状动脉狭窄的存在相关，但在多变量分析中不相关。MPO和CCL 5与冠心病无相关性，而IL 6 - 174 CC、SFTPD 11 CC和TLR 4299 AA等高危基因变异数与冠心病患者比例呈显著线性相关（P < 0.0005）。与炎症相关的遗传因素可能增加严重冠状动脉疾病的易感性。此外，来自不同炎症遗传标记的加性贡献强烈增强了心血管疾病的个体严重程度。
Inflammation plays a key role in the development of atherosclerosis. Genetic differences in molecules related to inflammation have therefore been linked to the susceptibility for and severity of atherosclerosis. We hypothesized that the additive contribution from different genes of importance for inflammation would enhance the severity of cardiovascular disease. Blood samples were collected from 230 adults admitted for elective coronary angiography. A total of 130 patients had significant (> 50%) stenosis in at least one main coronary artery branch and 100 had not. Six polymorphisms in five different genes were analysed: myeloperoxidase (MPO) -129G/A and -463G/A, toll-like receptor 4 (TLR4) Asp299Gly, interleukin-6 (IL6) -174G/C, surfactant protein D (SFTPD) Met11Thr and regulated upon normal T-cell expressed and secreted (CCL5) -403G/A. The IL6 polymorphism was significantly associated (P = 0.017) to angiographic significant coronary artery disease, and this relation remained after adjustment for age, gender, smoking and hypercholesterolaemia (P = 0.007). The TLR4 (P = 0.050) and SFTPD (P = 0.058) polymorphisms were also associated with the presence of coronary stenosis in univariate but not in multivariate analyses. For MPO and CCL5 no associations were found. There was a significant linear association between the number of high-risk gene variants (IL6-174CC, SFTPD 11CC and TLR4 299AA) and the proportion of patients with coronary artery disease (P < 0.0005). Inherited factors related to inflammation may increase susceptibility for severe coronary artery disease. Furthermore, the additive contribution from different inflammatory genetic markers strongly enhances the individual severity of cardiovascular disease.