title: Interleukin-10 haplotype associated with increased mortality in critically ill patients with sepsis from pneumonia but not in patients with extrapulmonary sepsis.
abstract: OBJECTIVE
  To test the hypothesis that haplotypes of the interleukin (IL)-10 gene are associated with clinical outcomes, comparing critically ill patients with sepsis from pneumonia vs those with extrapulmonary sepsis.
  
  
  METHODS
  Genetic association study.
  
  
  METHODS
  Medical/surgical ICUs in a tertiary-care, university-affiliated teaching hospital.
  
  
  METHODS
  Of 550 white patients with sepsis, 158 had pneumonia as the principle cause of their sepsis and 392 had an extrapulmonary source of sepsis.
  
  
  METHODS
  Haplotypes of the IL-10 gene were defined by measurement of haplotype tag single-nucleotide polymorphisms (SNPs). Primary outcome was 28-day survival. Secondary outcomes were days alive and free of organ dysfunction.
  
  
  RESULTS
  Three SNPs in the IL-10 gene (-592 C/A, +734 G/T, and +3367 G/A) identified four major haplotypes: CGG, AGG, CTA, and CTG. Patients with pneumonia who carried one or two copies of the CGG haplotype had greater 28-day mortality (51.4%) than patients who did not carry this haplotype (29.1%, p = 0.007). Carriers of CGG had significantly more cardiovascular dysfunction (and use of vasopressors), renal dysfunction (and requirement of dialysis), hepatic dysfunction, and hematologic dysfunction (p < 0.05 in each case). In contrast, in patients with an extrapulmonary source of infection there was no significant association of the CGG haplotype (or any measured IL-10 genotype) with 28-day mortality or organ dysfunction.
  
  
  CONCLUSIONS
  The IL-10 haplotype - 592C/734G/3367G is associated with increased mortality and organ dysfunction in critically ill patients with pulmonary sepsis but not in similarly ill patients with extrapulmonary sepsis. Therefore, polymorphisms within the IL-10 gene may be predictors of outcome in patients with sepsis from pneumonia.
authors.affiliation: Critical Care Research Laboratories, 1081 Burrard St, Vancouver, BC, Canada V6Z 1Y6.
authors.forename: Anan
authors.initials: A
authors.lastname: Wattanathum
authors.forename: Sanjay
authors.initials: S
authors.lastname: Manocha
authors.forename: Horacio
authors.initials: H
authors.lastname: Groshaus
authors.forename: James A
authors.initials: JA
authors.lastname: Russell
authors.forename: Keith R
authors.initials: KR
authors.lastname: Walley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness; D005260:Female; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000150:complications*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D018805:Sepsis / Q000209:etiology / Q000235:genetics* / Q000401:mortality*
chemical_list: D016753:Interleukin-10