title: The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study.
abstract: According to previous investigations, CD14 is suggested to play a pivotal role in initiating and perpetuating the pro-inflammatory response during sepsis. A functional polymorphism within the CD14 gene, rs2569190, has been shown to impact the pro-inflammatory response upon stimulation with lipopolysaccharide, a central mediator of inflammation in sepsis. In this study, we hypothesized that the strong pro-inflammatory response induced by the TT genotype of CD14 rs2569190 may have a beneficial effect on survival (30-day) in patients with sepsis. A total of 417 adult patients with sepsis (and of western European descent) were enrolled into this observational study. Blood samples were collected for rs2569190 genotyping. Patients were followed over the course of their stay in the ICU, and the 30-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure as a secondary variable. Moreover, organ support-free days were evaluated as a secondary outcome parameter. TT-homozygous patients were compared to C-allele carriers. Kaplan-Meier survival analysis revealed a higher 30-day mortality risk among C-allele carriers compared with T homozygotes (p = 0.0261). To exclude the effect of potential confounders (age, gender, BMI and type of infection) and covariates that varied at baseline with a p-value < 0.2 (e.g., comorbidities), we performed multivariate Cox regression analysis to examine the survival time. The CD14 rs2569190 C allele remained a significant covariate for the 30-day mortality risk in the multivariate analysis (hazard ratio, 2.11; 95% CI, 1.08-4.12; p = 0.0282). The 30-day mortality rate among C allele carriers was 23%, whereas the T homozygotes had a mortality rate of 13%. Additionally, an analysis of organ-specific SOFA scores revealed a significantly higher SOFA-Central nervous system score among patients carrying the C allele compared with T-homozygous patients (1.9±1.1 and 1.6±1.0, respectively; p = 0.0311). In conclusion, CD14 rs2569190 may act as a prognostic variable for the short-term outcome (30-day survival) in patients with sepsis.
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: Ashham
authors.initials: A
authors.lastname: Mansur
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Liese
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Steinau
authors.affiliation: Department of General and Visceral Surgery, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ghadimi
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bergmann
authors.affiliation: Institute of Clinical Pharmacology, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: Mladen
authors.initials: M
authors.lastname: Tzvetkov
authors.affiliation: Department of Cardiothoracic Transplantation & Mechanical Support, Royal Brompton and Harefield Hospital, Harefield, London, United Kingdom.
authors.forename: Aron Frederik
authors.initials: AF
authors.lastname: Popov
authors.affiliation: Department of Medical Statistics, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.
authors.forename: José
authors.initials: J
authors.lastname: Hinz
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D000483:Alleles; D018572:Disease-Free Survival; D006720:Homozygote; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000235:genetics / Q000401:mortality; D015996:Survival Rate
chemical_list: D018950:Lipopolysaccharide Receptors