Colín-Castro Claudia A, Franco-Cendejas Rafael, Rocha-González Hector I, Cruz-Arenas Esteban, Leyva-García Norberto, Sánchez-Sánchez Roberto, Leyva-Gomez Gerardo, Gómez Rocío, Muñoz Balam, Cortés Hernán, Magaña Jonathan J
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico.
Laboratory of Genomic Medicine, Department of Genetics, National Center for Research and Care for Burns (CENIAQ), Instituto Nacional de Rehabilitación-Luis Guillermo Ibarra Ibarra (INR-LGII), Mexico City, Mexico.
Genes Immun. 2021 May;22(1):24-34. doi: 10.1038/s41435-021-00121-z. Epub 2021 Feb 2.
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.
脓毒症是一种由对感染的失调反应引起的危及生命的器官功能障碍状况，在中度至重度烧伤患者中很常见。此前，关键的固有免疫受体Toll样受体4（TLR4）中的基因组变异已与脓毒症和感染易感性相关。在本研究中，在墨西哥混血人群中测试了六个TLR4单核苷酸多态性（SNP）与烧伤后脓毒症的关联。我们发现rs2737190多态性与烧伤创伤后脓毒症相关。有趣的是，G等位基因和GG基因型与发生脓毒症的较低风险相关。由于rs2737190 SNP位于TLR4基因的启动子区域，我们分析了这种多态性调节TLR4途径的可能性。我们培养了来自不同基因型携带者的外周血单个核细胞，在用脂多糖（LPS）刺激后发现，GG基因型携带者的TLR4、IL6和TNFα表达高于AA基因型携带者。结果表明，GG基因型使TLR4表达增加，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患者脓毒症遗传研究的有用标志物。
