Abstract
The aim of this study was to investigate the relationship between the CD14 rs2569190 polymorphism and death related to septic shock in white European patients who underwent major cardiac or abdominal surgery. We carried out a retrospective study in 205 septic shock patients. The septic shock diagnosis was established by international consensus definitions. The outcome variable was the death within 28, 60 and 90 days after septic shock diagnosis. The CD14 rs2569190 polymorphism was analyzed by Agena Bioscience’s MassARRAY platform. For the genetic association analysis with survival was selected a recessive inheritance model (GG vs. AA/AG). One hundred thirteen out of 205 patients (55.1%) died with a survival median of 39 days (95%CI = 30.6; 47.4). Patients with rs2569190 GG genotype had shorter survival probability than rs2569190 AA/AG genotype at 60 days (62.3% vs 50%; p = 0.035), and 90 days (62.3% vs 52.6%; p = 0.046). The rs2569190 GG genotype was associated with increased risk of septic shock-related death in the first 60 days (adjusted hazard ratio (aHR) = 1.67; p = 0.016) and 90 days (aHR = 1.64; p = 0.020) compared to rs2569190 AA/AG genotype. In conclusion, the presence of CD14 rs2569190 GG genotype was associated with death in shock septic patients who underwent major surgery. Further studies with bigger sample size are required to verify this relationship.
Highlights
Sepsis is a major cause of death from infection, mortality from sepsis has decreased due to improved supportive care and evidence-based guidelines for diagnosis and timely intervention[1,2]
We found a relationship between CD14 rs2569190 polymorphism and mortality in European septic shock patients who underwent major surgery
Patients with CD14 rs2569190 GG genotype had increased risk of death related to septic shock, suggesting that CD14 rs2569190 polymorphism may have an important function in the pathogenesis of septic shock
Summary
Sepsis is a major cause of death from infection, mortality from sepsis has decreased due to improved supportive care and evidence-based guidelines for diagnosis and timely intervention[1,2]. The stabilization of the clinical condition in septic patients is reached by the use of anti-infective treatments together to aggressive organ failure supports[1] These patients are susceptible to ICU-related complications, which have a notable repercussion on their early and late prognosis[5,6]. Multiple organ failure caused by the primary infection could mainly explain early deaths and ICU-related complications www.nature.com/scientificreports/. CD14, together with toll-like receptor 4 (TLR4) and lymphocyte antigen 96 (LY96, called MD-2), may bind LPS resulting in NF-kB activation and the production of proinflammatory cytokine[11] In this regard, there are a high number of genes, which are induced by NF-kB, that are implicated in the cellular response against infection and promote the synthesis of pro-inflammatory mediators. Several microRNAs have been involved in the NF-kB activity and modulation of the immune response, resulting in a worsening of the sepsis with developing of MODS and death[12]
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