De Staercke Christine, Lally Cathy, Austin Harland, Winston Carla, Dowling Nicole, Williams Byron, Hooper W Craig
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Thromb Res. 2007;119(1):105-10. doi: 10.1016/j.thromres.2005.12.010. Epub 2006 Feb 15.
The toll-like receptor 4 gene product (TLR4) has been implicated in the pathogen recognition response mechanism because it plays a central role in the transcriptional activation of the host defense system. Activation of TLR4 initiates an intracellular signaling cascade, via the adapter protein MyD88 (myeloid differentiation factor 88), which leads to the activation of NF-kappaB transcriptional factor, and ultimately to the induction of a pro-inflammatory response. This inflammatory response has been increasingly associated with atherosclerosis. Recent analyses on two polymorphisms of TLR4, which affect the extracellular domain of the receptor, have been shown to give rise to an attenuated innate immune defense which may contribute to disease susceptibility. We have investigated the significance of four new substitutions found by re-sequencing in the 5'-proximal promoter region of the TLR4 gene in a case-control study of acute myocardial infarction. Our results found no statistically significant association between these genetic variants and MI.
Toll样受体4基因产物（TLR4）参与了病原体识别反应机制，因为它在宿主防御系统的转录激活中起核心作用。TLR4的激活通过衔接蛋白MyD88（髓样分化因子88）启动细胞内信号级联反应，这导致核因子κB转录因子的激活，并最终引发促炎反应。这种炎症反应与动脉粥样硬化的关联日益密切。最近对TLR4的两种多态性进行的分析表明，这两种多态性影响受体的细胞外结构域，会导致先天性免疫防御减弱，这可能会增加疾病易感性。在一项急性心肌梗死的病例对照研究中，我们研究了通过重新测序在TLR4基因5'近端启动子区域发现的四个新替换的意义。我们的结果发现这些基因变异与心肌梗死之间没有统计学上的显著关联。
