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- Title
The regulatory toll-like receptor 4 genetic polymorphism rs11536889 is associated with renal, coagulation and hepatic organ failure in sepsis patients.
- Authors
Mansur, Ashham; Gruben, Luisa von; Popov, Aron F; Steinau, Maximilian; Bergmann, Ingo; Ross, Daniel; Ghadimi, Michael; Beissbarth, Tim; Bauer, Martin; Hinz, José; von Gruben, Luisa
- Abstract
<bold>Background: </bold>Toll-like receptor 4 (TLR4), a lipopolysaccharide (LPS) receptor complex signal-transducing molecule, plays a crucial role in sensing LPS from gram-negative bacteria. TLR4 signaling pathway activation by LPS plays a major role in sepsis pathogenesis. A single nucleotide polymorphism, rs11536889, in the 3'-untranslated region of the TLR4 gene is thought to affect TLR4 translation. This study aimed to investigate whether organ failure in sepsis patients is related to the TLR4 rs11536889 genotype.<bold>Methods: </bold>Adult Caucasian patients with sepsis from the intensive care unit of a university medical center were followed up for 90 days, and organ failure was recorded as the primary outcome variable. Blood samples were collected at enrollment for TLR4 rs11536889 genotyping. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure.<bold>Results: </bold>A total of 210 critically ill patients with sepsis were enrolled into this study. Wild-type GG was compared to GC/CC. During their stay in the intensive care unit, GG patients presented significantly higher SOFA scores than did C allele carriers (7.9 ± 4.5 and 6.8 ± 4.2, respectively; p = 0.0005). Analysis of organ-specific SOFA sub-scores revealed significant differences in three organ systems: renal, coagulation and hepatic (p = 0.0005, p = 0.0245 and p < 0.0001, respectively). Additionally, the rs11536889 polymorphism was associated with a higher incidence of gram-negative infections.<bold>Conclusions: </bold>These results offer the first evidence that TLR4 rs11536889 is a useful marker of organ failure in patients with sepsis.
- Publication
Journal of Translational Medicine, 2014, Vol 12, Issue 1, p177
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/1479-5876-12-177