Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections
Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections
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DOI：
10.1086/344893
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发表时间：
2002-11-15
影响因子：
6.4
通讯作者：
Lowry, SF
中科院分区：
文献类型：
--
作者：
Agnese, DM;Calvano, JE;Lowry, SF
已知人toll样受体4（hTLR 4）和CD 14是脂多糖受体复合物的组分。我们的研究调查了TLR 4突变（Asp 299 Gly和Thr 399 Ile）和CD 14多态性与重症监护病房（ICU）脓毒症风险人群结局之间的关系。通过使用基于聚合酶链反应的限制性片段长度多态性分析技术，hTLR 4基因在14（18%）的77例ICU患者（均为全身炎症反应综合征阳性）和5（13%）的39名志愿者中发生改变。与野生型人群（11/63; P = 0.004）相比，携带突变的患者（11/14）的革兰氏阴性菌感染发生率显著更高（11/14; P = 0.004）。未观察到CD 14多态性与感染发生率或结局之间的相关性。这些发现表明，hTLR 4突变与手术环境中危重患者革兰氏阴性感染发生率的增加有关。
Human toll-like receptor 4 (hTLR4) and CD14 are known to be components of the lipopolysaccharide receptor complex. Our study investigated the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphism(s) with outcome in an intensive care unit (ICU) population at risk for sepsis. By use of a polymerase chain reaction-based restriction fragment-length polymorphism analysis technique, the hTLR4 gene was altered in 14 (18%) of 77 ICU patients (all positive for systemic inflammatory response syndrome) and in 5 (13%) of 39 volunteers. There was a significantly higher incidence of gram-negative infection among patients with the mutations (11 [79%] of 14), compared with that in the wildtype population (11 [17%] of 63; P = .004). No association between CD14 polymorphism(s) and the incidence of infection or outcome was observed. These findings indicate that hTLR4 mutations are associated with an increased incidence of gram-negative infections in critically ill patients in a surgical setting.