TY - JOUR
T1 - Association of TLR4 gene polymorphisms with sepsis after a burn injury
T2 - findings of the functional role of rs2737190 SNP
AU - Colín-Castro, Claudia A.
AU - Franco-Cendejas, Rafael
AU - Rocha-González, Hector I.
AU - Cruz-Arenas, Esteban
AU - Leyva-García, Norberto
AU - Sánchez-Sánchez, Roberto
AU - Leyva-Gomez, Gerardo
AU - Gómez, Rocío
AU - Muñoz, Balam
AU - Cortés, Hernán
AU - Magaña, Jonathan J.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85100287613&partnerID=8YFLogxK
U2 - 10.1038/s41435-021-00121-z
DO - 10.1038/s41435-021-00121-z
M3 - Artículo
C2 - 33531683
AN - SCOPUS:85100287613
SN - 1466-4879
VL - 22
SP - 24
EP - 34
JO - Genes and Immunity
JF - Genes and Immunity
IS - 1
ER -