Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections

被引:435
作者
Agnese, DM [1 ]
Calvano, JE [1 ]
Hahm, SJ [1 ]
Coyle, SM [1 ]
Corbett, SA [1 ]
Calvano, SE [1 ]
Lowry, SF [1 ]
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, Div Surface Sci, New Brunswick, NJ 08903 USA
关键词
D O I
10.1086/344893
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页码:1522 / 1525
页数:4
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