Clinical Relevance of the TLR4 11367 Polymorphism in Patients With Major Trauma
Clinical Relevance of the TLR4 11367 Polymorphism in Patients With Major Trauma
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DOI：
10.1001/archsurg.2009.211
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发表时间：
2009-12-01
影响因子：
--
通讯作者：
Jiang, Jian-xin
中科院分区：
文献类型：
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作者：
Duan, Zhao-xia;Gu, Wei;Jiang, Jian-xin
目的：探讨TLR4 11367多态性在重大创伤患者中的临床相关性。设计：遗传功能及关联研究。地点：中国重庆市大坪医院和重庆急救中心。患者：前瞻性招募132例重大创伤患者。主要指标：采用单管、双向、等位基因特异性扩增方法对TLR4 11367多态性进行基因分型。入院后 24 小时内获得的全外周血样本用脂多糖刺激，然后检测肿瘤坏死因子 a 和白细胞介素 6 的产生。评估脓毒症发病率和多器官功能障碍评分。结果：11367 多态性与入院时创伤患者响应离体脂多糖刺激而外周白细胞产生肿瘤坏死因子 a 和白细胞介素 6 的能力降低密切相关。关联研究的结果表明，携带11367C等位基因的创伤患者患脓毒症和多器官功能障碍的可能性较小。结论：结合我们之前的体外功能研究，结果表明，TLR4 11367多态性可能是一个很好的预测因子，可以根据基因型判断谁更有可能出现脓毒症或多器官功能障碍综合征等并发症。
Objective: To investigate the clinical relevance of the TLR4 11367 polymorphism in patients with major trauma.Design: Genetic functional and association study.Setting: Daping Hospital and Chongqing Emergency Medical Center, Chongqing, China.Patients: A total of 132 patients with major trauma were prospectively recruited.Main Outcome Measures: The TLR4 11367 polymorphism was genotyped using single-tube, bidirectional, allele-specific amplification method. Whole peripheral blood samples obtained within 24 hours after admission were stimulated with lipopolysaccharide and then tested for production of tumor necrosis factor a and interleukin 6. Sepsis morbidity rate and multiple organ dysfunction scores were assessed.Results: The 11367 polymorphism, was shown to be strongly associated with less capacity of peripheral leukocytes to produce tumor necrosis factor a and interleukin 6 in response to ex vivo lipopolysaccharide stimulation in patients with trauma at admission. Results from association study indicated that patients with trauma who carry the 11367C allele were less likely to have sepsis and multiple organ dysfunction.Conclusions: Combined with our previous in vitro functional study, the results suggest that the TLR4 11367 polymorphism might be a good predictor of who is more likely to develop complications such as sepsis or multiple organ dysfunction syndrome, depending on genotype.