Association of TLR4 gene polymorphisms with sepsis after a burn injury: findings of the functional role of rs2737190 SNP
Por:
Colin-Castro, Claudia A., Franco-Cendejas, Rafael, Rocha-Gonzalez, I, Hector, Cruz-Arenas, Esteban, Leyva-Garcia, Norberto, Sanchez-Sanchez, Roberto, Leyva-Gomez, Gerardo, Gomez, Rocio, Munoz, Balam, Cortes, Hernan, Magana, Jonathan J.
Publicada:
1 may 2021
Ahead of Print:
1 feb 2021
Resumen:
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 TNF
alpha 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.
Filiaciones:
Colin-Castro, Claudia A.:
Rocha-Gonzalez, Hector, I, Inst Politecn Nacl, Escuela Super Med, Secc Estudios Posgrad & Invest, Mexico City, DF, Mexico
Inst Nacl Rehabil Luis Guillermo Ibarra Ibarra IN, Natl Ctr Res & Care Burns CENIAQ, Dept Genet, Lab Genom Med, Mexico City, DF, Mexico
Franco-Cendejas, Rafael:
INR LGII, CENIAQ, Dept Infectol, Mexico City, DF, Mexico
Cruz-Arenas, Esteban:
INR LGII, Epidemiol Surveillance Unit, Mexico City, DF, Mexico
Leyva-Garcia, Norberto:
Inst Nacl Rehabil Luis Guillermo Ibarra Ibarra IN, Natl Ctr Res & Care Burns CENIAQ, Dept Genet, Lab Genom Med, Mexico City, DF, Mexico
Sanchez-Sanchez, Roberto:
INR LGII, Dept Biotechnol, CENIAQ, Mexico City, DF, Mexico
Leyva-Gomez, Gerardo:
Univ Nacl Autonoma Mexico, Chem Fac, Dept Pharm, Mexico City, DF, Mexico
Gomez, Rocio:
CINVESTAV IPN, Dept Toxicol, Mexico City, DF, Mexico
Munoz, Balam:
Sch Engn & Sci, Dept Bioengn, Tecnol Monterrey Campus Ciudad Mexico ITESM CCM, Mexico City, DF, Mexico
Cortes, Hernan:
Inst Nacl Rehabil Luis Guillermo Ibarra Ibarra IN, Natl Ctr Res & Care Burns CENIAQ, Dept Genet, Lab Genom Med, Mexico City, DF, Mexico
Magana, Jonathan J.:
Inst Nacl Rehabil Luis Guillermo Ibarra Ibarra IN, Natl Ctr Res & Care Burns CENIAQ, Dept Genet, Lab Genom Med, Mexico City, DF, Mexico
Sch Engn & Sci, Dept Bioengn, Tecnol Monterrey Campus Ciudad Mexico ITESM CCM, Mexico City, DF, Mexico
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