State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Chongqing, China.
Shock. 2011 Jan;35(1):35-41. doi: 10.1097/SHK.0b013e3181eb45b3.
Toll-like receptor 2 (TLR2) signaling plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire TLR2 gene and to investigate their clinical relevance in patients with major trauma. A total of 410 patients with major trauma were prospectively recruited. The htSNPs of the TLR2 gene was determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipoprotein and then determined for production of tumor necrosis factor-α, interleukin 8, and interleukin 10. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs1898830, rs3804099, and rs7656411) were identified as htSNPs for the TLR2 gene. All of them were shown to be high-frequency SNPs in this study cohort. Two of them (rs1898830 and rs3804099) and the haplotype ATT were significantly associated with cytokine production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Only rs3804099, however, was significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma. In addition, the patients with the haplotype ATT had lower sepsis morbidity rate than those without the haplotype ATT. Therefore, three SNPs might act as htSNPs for the entire TLR2 gene in the Chinese population. The rs3804099 and the haplotype ATT might be used as relevant risk estimates for the development of sepsis and MOD in patients with major trauma.
Toll 样受体 2（TLR2）信号在协调先天免疫反应以及创伤后脓毒症和随后的器官功能障碍的发展中起着关键作用。本前瞻性研究的目的是确定整个 TLR2 基因中的单核苷酸多态性（SNP）标签，并探讨其在重大创伤患者中的临床相关性。共前瞻性招募了 410 名重大创伤患者。使用 HapMap 数据库和连锁不平衡分析确定 TLR2 基因的 htSNP。使用聚合酶链反应-限制性片段长度多态性方法对 htSNP 进行基因分型。入院后立即采集全血样本，用细菌脂蛋白刺激，然后测定肿瘤坏死因子-α、白细胞介素 8 和白细胞介素 10 的产生量。评估脓毒症发病率和多器官功能障碍（MOD）评分。确定了三个 SNP（rs1898830、rs3804099 和 rs7656411）作为 TLR2 基因的 htSNP。所有这些 SNP 在本研究队列中均为高频 SNP。其中两个（rs1898830 和 rs3804099）和 ATT 单倍型与细菌脂蛋白刺激外周血白细胞产生细胞因子显著相关。然而，只有 rs3804099 与重大创伤患者更高的脓毒症发病率和 MOD 评分显著相关。此外，具有 ATT 单倍型的患者脓毒症发病率低于无 ATT 单倍型的患者。因此，这三个 SNP 可能作为中国人群整个 TLR2 基因的 htSNP。rs3804099 和 ATT 单倍型可能作为重大创伤患者脓毒症和 MOD 发展的相关风险估计。
