title: Association of REL polymorphisms and outcome of patients with septic shock.
abstract: BACKGROUND
  cRel, a subunit of NF-κB, is implicated in the inflammatory response observed in autoimmune disease. Hence, knocked-out mice for cRel had a significantly higher mortality, providing new and important functions of cRel in the physiopathology of septic shock. Whether genetic variants in the human REL gene are associated with severity of septic shock is unknown.
  
  
  METHODS
  We genotyped a population of 1040 ICU patients with septic shock and 855 ICU controls for two known polymorphisms of REL; REL rs842647 and REL rs13031237. Outcome of patients according to the presence of REL variant alleles was compared.
  
  
  RESULTS
  The distribution of REL variant alleles was not significantly different between patients and controls. Among the septic shock group, REL rs13031237*T minor allele was not associated with worse outcome. In contrast, REL rs842647*G minor allele was significantly associated with more multi-organ failure and early death [OR 1.4; 95 % CI (1.02-1.8)].
  
  
  CONCLUSIONS
  In a large ICU population, we report a significant clinical association between a variation in the human REL gene and severity and mortality of septic shock, suggesting for the first time a new insight into the role of cRel in response to infection in humans.
authors.affiliation: Medical School, Paris Descartes University, Paris, France. julie.toubiana@aphp.fr.|INSERM U1016, CNRS UMR 8104, Cochin Institute, Paris, France. julie.toubiana@aphp.fr.|Department of Pediatric and Infectious Diseases, Necker University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. julie.toubiana@aphp.fr.
authors.forename: Julie
authors.initials: J
authors.lastname: Toubiana
authors.affiliation: Medical School, Paris Descartes University, Paris, France.|INSERM U1016, CNRS UMR 8104, Cochin Institute, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Courtine
authors.affiliation: Bioinformatics Platform, Institut Imagine, Paris Descartes University- Sorbonne Paris Cité, 75015, Paris, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Tores
authors.affiliation: Medical Intensive Care Unit, Angers University Hospital, Angers, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.affiliation: Medical Intensive Care, Caen University Hospital, Caen, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Daubin
authors.affiliation: INSERM U1016, CNRS UMR 8104, Cochin Institute, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rousseau
authors.affiliation: INSERM U1016, CNRS UMR 8104, Cochin Institute, Paris, France.
authors.forename: Fatah
authors.initials: F
authors.lastname: Ouaaz
authors.affiliation: Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Marin
authors.affiliation: Medical School, Paris Descartes University, Paris, France.|Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Cariou
authors.affiliation: Medical School, Paris Descartes University, Paris, France.|INSERM U1016, CNRS UMR 8104, Cochin Institute, Paris, France.|Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Chiche
authors.affiliation: Medical School, Paris Descartes University, Paris, France.|INSERM U1016, CNRS UMR 8104, Cochin Institute, Paris, France.|Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
keywords: Genetics; Mortality; Multi-organ dysfunction syndrome; Polymorphism; REL; Septic shock; cRel