Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock
Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock
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DOI：
10.1001/archinte.162.9.1028
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发表时间：
2002-05-13
影响因子：
--
通讯作者：
Schwartz, DA
中科院分区：
文献类型：
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作者：
Lorenz, E;Mira, JP;Schwartz, DA
背景资料：脓毒性休克仍然是世界范围内的一个重大健康问题，尽管在了解脓毒性休克的生理和分子基础方面取得了进展，但脓毒性休克患者的高死亡率仍然没有改变。我们最近发现了Toll样受体4（TLR 4）的一种常见多态性，该多态性与人体对吸入内毒素或脂多糖的低反应性有关。由于TLR 4是哺乳动物中脂多糖的主要受体，而革兰氏阴性菌是感染性休克的主要病原体，我们研究了这些特异性TLR 4等位基因是否与感染性休克患者更严重疾病结局的易感性相关。我们对91例感染性休克患者以及73例健康献血者对照进行了TLR 4 Asp 299 Gly和TLR 4 Thr 399 Ile突变的基因分型，结果：我们发现TLR 4 Asp 299 Gly等位基因仅见于感染性休克患者（P= 0.05）。此外，与TLR 4 Asp 299 Gly/Thr 399 Ile等位基因感染性休克的患者有较高的患病率革兰氏阴性infectious.Conclusion：TLR 4受体的突变可能使人们更容易发展感染性休克与革兰氏阴性微生物。
Background: Septic shock remains a significant health concern worldwide, and despite progress in understanding the physiological and molecular basis of septic shock, the high mortality rate of patients with septic shock remains unchanged. We recently identified a common polymorphism in toll-like receptor 4 (TLR4) that is associated with hyporesponsiveness to inhaled endotoxin or lipopolysaccharide in humans.Methods: Since TLR4 is a major receptor for lipopolysaccharide in mammals and gram-negative bacteria are the prevalent pathogen associated with septic shock, we investigated whether these specific TLR4 alleles are associated with a predisposition to a more severe disease outcome for patients with septic shock. We genotyped 91 patients with septic shock as well as 73 healthy blood donor controls for the presence of the TLR4 Asp299Gly and TLR4 Thr399Ile mutations.Results: We found the TLR4 Asp299Gly allele exclusively in patients with septic shock (P=.05). Furthermore, patients with septic shock with the TLR4 Asp299Gly/Thr399Ile alleles had a higher prevalence of gram-negative infections.Conclusion: Mutations in the TLR4 receptor may predispose people to develop septic shock with gram-negative microorganisms.