Agnese Doreen M, Calvano Jacqueline E, Hahm Sae J, Coyle Susette M, Corbett Siobhan A, Calvano Steve E, Lowry Stephen F
Division of Surgical Sciences, Department of Surgery, University of Medicine and Dentistry New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
J Infect Dis. 2002 Nov 15;186(10):1522-5. doi: 10.1086/344893. Epub 2002 Oct 29.
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 wild-type 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.
已知人类 Toll 样受体 4（hTLR4）和 CD14 是脂多糖受体复合物的组成部分。我们的研究调查了 TLR4 突变（Asp299Gly 和 Thr399Ile）及 CD14 多态性与脓毒症风险重症监护病房（ICU）人群预后之间的关联。通过基于聚合酶链反应的限制性片段长度多态性分析技术，77 例 ICU 患者（均为全身炎症反应综合征阳性）中有 14 例（18%）以及 39 名志愿者中有 5 例（13%）的 hTLR4 基因发生改变。与野生型人群（63 例中的 11 例[17%]）相比，发生突变的患者中革兰氏阴性菌感染的发生率显著更高（14 例中的 11 例[79%]；P = 0.004）。未观察到 CD14 多态性与感染发生率或预后之间存在关联。这些发现表明，在外科环境下，hTLR4 突变与重症患者革兰氏阴性菌感染发生率增加有关。
