title: IL-6 rs1800795 polymorphism is associated with septic shock-related death in patients who underwent major surgery: a preliminary retrospective study.
abstract: BACKGROUND
  Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, being the primary cause of death from infection, especially if not recognized and treated promptly. The aim of this study was to analyze whether IL-6 rs1800795 polymorphism is associated with septic shock-related death in European white patients who underwent major surgery.
  
  
  METHODS
  We performed a retrospective study on 202 septic shock patients who underwent major cardiac or abdominal surgery. The septic shock was established according to the international septic shock definition. The primary outcome variable was the death within 90 days after diagnosis of septic shock. The IL-6 rs1800795 polymorphism was genotyped by Sequenom's MassARRAY platform.
  
  
  RESULTS
  The median age of the patients was 73 years, 63.4% were male, and more than 40% of patients had heart disease and hypertension. Overall, the survival analysis showed that 111 (55%) patients died with a survival median of 39 days (95% CI 30.7; 47.2). The genetic analysis association with survival was performed under a recessive genetic model (CC vs. GG/CG). Patients with IL-6 rs1800795 CC genotype had higher mortality rate than the IL-6 rs1800795 GG/CG genotype at days 7 [31.6% (6/19) vs. 10.4% (19/183); log-rank test (p = 0.005)] and 28 [57.9% (11/19) vs. 33.3% (61/183); log-rank test (p = 0.009)], and 90 [68.4% (13/19) vs. 53.5% (98/183); log-rank test (p = 0.006)]. The IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death during the first 7 days [adjusted hazard ratio (aHR 4.65; p = 0.002), 28 days (aHR 2.50; p = 0.006), and 90 days (aHR 2.28; p = 0.006)] with septic shock. When patients were stratified by type of surgery, those with IL-6 rs1800795 CC genotype who underwent cardiac surgery had higher risk of death during the first 7 days (aHR 18.39; p = 0.001) and 28 days (aHR 6.1; p = 0.025) than IL-6 rs1800795 GG/GC carrier, whereas patients with IL-6 rs1800795 CC genotype who underwent abdominal surgery had higher risk of death during all follow-up (aHR 1.98; p = 0.050) than IL-6 rs1800795 GG/GC carrier.
  
  
  CONCLUSIONS
  The presence of IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death in patients who underwent major cardiac or abdominal surgery. These findings need robust validation in bigger independent cohorts.
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain. majimenezsousa@yahoo.es.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Jiménez-Sousa
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
authors.forename: Luz Maria
authors.initials: LM
authors.lastname: Medrano
authors.affiliation: Departamento de Anestesiología y Reanimación, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Liu
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
authors.forename: Amanda
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.affiliation: Unidad de Investigación Médica en Infección e Inmunidad, Hospital Clínico Universitario-IECSCYL, Valladolid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Almansa
authors.affiliation: Departamento de Anestesiología y Reanimación, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Gomez-Sanchez
authors.affiliation: Unidad de Investigación Médica en Infección e Inmunidad, Hospital Clínico Universitario-IECSCYL, Valladolid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Departamento de Anestesiología y Reanimación, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Heredia-Rodríguez
authors.affiliation: Departamento de Anestesiología y Reanimación, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Gómez-Pesquera
authors.affiliation: Departamento de Anestesiología y Reanimación, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tamayo
authors.affiliation: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain. sresino@isciii.es.
authors.forename: Salvador
authors.identifier: http://orcid.org/0000-0001-8783-0450
authors.initials: S
authors.lastname: Resino
keywords: IL-6; Major surgery; SNPs; Septic shock; Survival