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Association of TLR4 gene polymorphisms with sepsis after a burn injury: findings of the functional role of rs2737190 SNP

Genes & Immunity volume 22, pages 24–34 (2021)Cite this article

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Abstract

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.

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Fig. 1: Schematic representation of the human TLR4 gene.
Fig. 2: Disturbances in pro-inflammatory cytokines in the TLR4 pathway.
Fig. 3: RT-PCR and qRT-PCR expression of TLR4.

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Acknowledgements

This work was supported by CONACyT-México (grant number 2013-01-201918) to JJM. CACC is a doctoral student from the Doctorado en Investigación en Medicina program at the Instituto Politécnico Nacional (IPN)-Escuela Superior de Medicina in Mexico.

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Authors and Affiliations

  1. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico

    Claudia A. Colín-Castro & Hector I. Rocha-González

  2. 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

    Claudia A. Colín-Castro, Norberto Leyva-García, Hernán Cortés & Jonathan J. Magaña

  3. Department of Infectology, CENIAQ, INR-LGII, Mexico City, Mexico

    Rafael Franco-Cendejas

  4. Epidemiological Surveillance Unit, INR-LGII, Mexico City, Mexico

    Esteban Cruz-Arenas

  5. Department of Biotechnology, CENIAQ, INR-LGII, Mexico City, Mexico

    Roberto Sánchez-Sánchez

  6. Department of Pharmacy, Chemistry Faculty, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Gerardo Leyva-Gomez

  7. Department of Toxicology, CINVESTAV-IPN, Mexico City, Mexico

    Rocío Gómez

  8. School of Engineering and Sciences, Department of Bioengineering, Tecnologico de Monterrey-Campus Ciudad de México (ITESM-CCM), Mexico City, Mexico

    Balam Muñoz & Jonathan J. Magaña

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  1. Claudia A. Colín-Castro
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Colín-Castro, C.A., Franco-Cendejas, R., Rocha-González, H.I. et al. Association of TLR4 gene polymorphisms with sepsis after a burn injury: findings of the functional role of rs2737190 SNP. Genes Immun 22, 24–34 (2021). https://doi.org/10.1038/s41435-021-00121-z

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