Toll-like receptor (TLR)-9 promotor polymorphisms and atherosclerosis
Toll-like receptor (TLR)-9 promotor polymorphisms and atherosclerosis
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DOI：
10.1016/j.cca.2005.07.017
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发表时间：
2006-02-01
影响因子：
5
通讯作者：
Schumann, RR
中科院分区：
文献类型：
--
作者：
Hamann, L;Glaeser, C;Schumann, RR
背景资料：目前，动脉粥样硬化的主要原因仍然存在争议：虽然氧化或酶促改变的LDL被广泛认为是炎症病变的原因之一，但微生物如C。肺炎病毒或巨细胞病毒（CMV）最近也被假定参与动脉粥样硬化的发病机制。微生物产品通过Toll样受体（TLR）激活宿主的先天免疫细胞。TLR-2和TLR-4基因的常见多态性已被证明分别与PTCA后再狭窄风险增加和颈动脉粥样硬化风险降低相关。微生物DNA已显示通过胞质TLR-9激活免疫细胞。特别是肺炎衣原体和巨细胞病毒作为细胞内病原体，可能是TLR-9信号转导的强有力触发剂。因此，我们研究TLR-9基因的两个常见启动子多态性是否与动脉粥样硬化形成相关。采用真实的时间PCR方法对202名汉族人群进行T-1237 C和T-1486 C多态性分析（衍生研究，年龄58.1，SD 10.0）和182（验证研究，年龄59.7，SD 9.6）接受血管成形术的患者和188名健康对照（年龄52.5，SD 6.1）。结果：我们发现TLR-9启动子的两个多态性能够为转录因子创造新的潜在结合位点，但与动脉粥样硬化形成或再狭窄没有关联。结论：我们的数据表明TLR-9启动子的两个多态性不参与动脉粥样硬化的形成。(C)2005 Elsevier B. V.保留所有权利。
Background: Currently, the primary cause of atherosclerosis remains controversial: while oxidized or enzymatically altered LDL is widely accepted as one cause of the inflamed lesion, microorganisms such as C. pneumoniae or cytomegalovirus (CMV) also have recently been postulated to be involved in the pathogenesis of atherosclerosis. Microbial products activate innate immune cells of the host via Toll-like receptors (TLRs). Common polymorphisms of the TLR-2 and TLR-4 genes have been shown to be associated with an increased risk for restenosis after PTCA, and a lower risk of carotid atherosclerosis, respectively. Microbial DNA has been shown to activate immune cells via the cytosolic TLR-9. Specially, C pneumonia and CMV as intracellular pathogens may be potent trigger of TLR-9 signaling. Therefore, we investigated whether the two common promotor polymorphisms of the TLR-9 gene are correlated with atherogenesis.Methods: The T-1237C and the T-1486C polymorphisms were analyzed by Real Time PCR in 202 (derivation study, age 58.1, SD 10.0) and 182 (validation study, age 59.7, SD 9.6) patients that underwent angioplasty and 188 healthy controls (age 52.5, SD 6.1). Restenosis was defined as >50% luminal diameter reduction at follow-up angiography.Results: We found the two polymorphism being able to create new potential binding sites for transcription factors, however, no association of the TLR-9 polymorphisms with atherogenesis or restenosis was detectable.Conclusion: Our data indicate that the two TLR-9 promotor polymorphisms are not involved in atherogenesis. (C) 2005 Elsevier B.V. All rights reserved.