Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients
Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients
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DOI：
10.1016/j.jss.2005.05.020
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发表时间：
2005-12-01
影响因子：
2.2
通讯作者：
Tokuhisa, T
中科院分区：
文献类型：
--
作者：
Nakada, T;Hirasawa, H;Tokuhisa, T
微生物组分的先天识别和随后的细胞因子网络的激活在脓毒症的病理生理学中是重要的。最近，与这些反应相关的分子中的功能基因多态性被证明。另一方面，有人声称，在遗传多态性方面存在种族差异。本研究调查了197名日本重症患者和214名健康对照受试者的Toll样受体（TLR）4、CD 14、肿瘤坏死因子（TNF）-α和-β以及白细胞介素（IL）-10基因多态性，以评估这些多态性对临床结局的影响。未检测到携带TLR 4Asp 299 Gly或Thr 399 Ile的日本受试者。未观察到CD 14 - 159 C/T多态性与基因型频率或脓毒症死亡率相关。脓毒症组TNF-α-308 GA基因型频率显著高于对照组，TNF-α-308 GA和IL-10- 592 CC基因型与脓毒症不良结局相关。遗传变异的种族差异是非常重要的问题，本研究中的频率与以前报道的高加索人不同。总之，这项研究可能表明，TNF-α-308 G/A和IL-10- 592 C/A多态性参与随后的细胞因子网络激活对脓毒症患者的临床结局的影响大于TLR 4Asp 299 Gly，Thr 399 Ile和CD 14 - 159 C/T多态性与初始宿主-微生物相互作用。(c)2005年爱思唯尔公司All rights reserved.
The innate recognition of microbial components and subsequent activation of cytokine network are important in the pathophysiology of sepsis. Recently, functional gene polymorphisms in molecules associated with these responses were demonstrated. On the other hand, it has been claimed that there are ethnic differences in genetic polymorphisms. This study investigated toll-like receptor (TLR) 4, CD14, tumor necrosis factor (TNF)-alpha and -beta, and interleukin (IL)-10 gene polymorphisms in 197 Japanese critically ill patients and 214 healthy control subjects to evaluate the influence of these polymorphisms on clinical outcome. No Japanese participant carrying TLR4Asp299Gly or Thr399Ile was detected. No association of CD14-159C/T polymorphisms with genotype frequency or sepsis mortality was observed. Frequency of TNF-alpha-308 GA genotype was significantly higher in the sepsis group than in the control group and TNF-alpha-308GA and IL-10-592CC genotypes were related to poor outcome of sepsis. Ethnic differences in genetic variations are very important issues and the frequencies in this study differ from those previously reported in Caucasians. In conclusion, this study may indicate that TNF-alpha-308G/A and IL-10-592C/A polymorphisms involved in subsequent activation of cytokine network had a larger effect on clinical outcome in patients with sepsis than TLR4Asp299Gly, Thr399Ile, and CD14-159C/T polymorphisms associated with the initial host-microbial interaction. (c) 2005 Elsevier Inc. All rights reserved.