State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Chongqing, China.
Br J Surg. 2011 Sep;98(9):1252-9. doi: 10.1002/bjs.7532. Epub 2011 Jun 1.
Toll-like receptor (TLR) 9 is the pattern recognition receptor for microbial DNA. Genetic variation within pattern recognition receptors for bacterial endotoxin and exotoxin has been shown to be associated with the risk of sepsis and organ dysfunction in critical illness. However, little is known about the clinical relevance of TLR9 gene polymorphisms in critical illness.
A total of 557 patients with major blunt trauma were included in the study. Genetic variation data for the entire TLR9 gene were obtained from the HapMap Project. The genotypes of TLR9 gene polymorphisms were determined using a pyrosequencing method. Whole peripheral blood samples obtained immediately after admission were stimulated with bacterial DNA and production of tumour necrosis factor (TNF) α was then determined. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were assessed.
Of five single-nucleotide polymorphisms (SNPs) genotyped, four (rs187084, rs352139, rs352140 and rs352162) existed as common SNPs and were in strong linkage disequilibrium. Both rs187084 and rs352162 were significantly associated with TNF-α production by peripheral blood leucocytes in response to bacterial DNA stimulation and a higher sepsis morbidity rate in patients with major trauma. In addition, the rs352162 polymorphism was significantly associated with MOD scores, whereas rs187084 showed a trend to be associated with MOD score.
TLR9 polymorphisms rs187084 and rs352162 might be used to provide relevant risk estimates for the development of sepsis and MOD in patients with major trauma.
Toll 样受体（TLR）9 是微生物 DNA 的模式识别受体。细菌内毒素和外毒素的模式识别受体的遗传变异已被证明与危重病患者败血症和器官功能障碍的风险相关。然而，TLR9 基因多态性在危重病中的临床相关性知之甚少。
本研究共纳入 557 例主要钝性创伤患者。从 HapMap 项目中获得了整个 TLR9 基因的遗传变异数据。使用焦磷酸测序法确定 TLR9 基因多态性的基因型。入院后立即采集全外周血样本，用细菌 DNA 刺激，然后测定肿瘤坏死因子（TNF）α的产生。评估败血症发病率和多器官功能障碍（MOD）评分。
在所检测的五个单核苷酸多态性（SNP）中，有四个（rs187084、rs352139、rs352140 和 rs352162）为常见 SNP，且紧密连锁。rs187084 和 rs352162 均与外周血白细胞对细菌 DNA 刺激产生 TNF-α的能力显著相关，且与严重创伤患者的败血症发病率升高相关。此外，rs352162 多态性与 MOD 评分显著相关，而 rs187084 与 MOD 评分呈显著相关趋势。
TLR9 多态性 rs187084 和 rs352162 可用于为严重创伤患者发生败血症和 MOD 提供相关风险估计。
