Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated response to an infection that is common among patients with moderate to severe burn injury. Previously, genomic variants in Toll-like receptor 4 (TLR4), a key innate immunity receptor, have been associated with sepsis and infection susceptibility. In this study, the association of six TLR4 SNPs with sepsis after burn injury was tested in the Mexican mestizo population. We found that the rs2737190 polymorphism is associated with sepsis after burn trauma. Interestingly, the G allele and GG genotype were associated with a lower risk of developing sepsis. Since the rs2737190 SNP is in the promoter region of the TLR4 gene, we analyzed the possibility that this polymorphism regulates the TLR4 pathway. We cultured peripheral blood mononuclear cells from different genotype carriers and found, after stimulation with LPS, that carriers of the GG genotype showed a higher expression of TLR4, IL6, and TNFα than AA genotype carriers. The results suggest that the GG genotype produces an increase in the TLR4 expression, and therefore an improvement in the immune response. We conclude that the rs2737190 polymorphism may become a useful marker for genetic studies of sepsis in patients after a burn injury.

脓毒症是一种危及生命的器官功能障碍，由对感染的反应失调引起，在中度至重度烧伤患者中很常见。以前，Toll 样受体 4 (TLR4)（一种关键的先天免疫受体）的基因组变异与败血症和感染易感性有关。在这项研究中，在墨西哥混血人群中测试了六个TLR4 SNP 与烧伤后败血症的关联。我们发现 rs2737190 多态性与烧伤后败血症有关。有趣的是，G 等位基因和 GG 基因型与发生败血症的风险较低有关。由于 rs2737190 SNP 位于TLR4的启动子区域基因，我们分析了这种多态性调节 TLR4 通路的可能性。我们培养了不同基因型携带者的外周血单个核细胞，发现在用LPS刺激后，GG基因型携带者比AA基因型携带者表现出更高的TLR4、IL6和TNFα表达。结果表明，GG 基因型会增加TLR4表达，从而改善免疫反应。我们得出结论，rs2737190 多态性可能成为烧伤后败血症患者遗传学研究的有用标记。