title: An NFKB1 promoter insertion/deletion polymorphism influences risk and outcome in acute respiratory distress syndrome among Caucasians.
abstract: BACKGROUND
  Nuclear factor-κB (NF-κB) is required for transcription of many pro-inflammatory genes and has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We hypothesized that a known functional polymorphism in the promoter of the NFKB1 gene may affect susceptibility to and outcome from ARDS.
  
  
  METHODS
  A case control study was conducted among a cohort of patients admitted to the intensive care unit (ICU) with risk factors for the development of ARDS. 379 patients with ARDS and 793 at-risk controls were studied. Patients were followed for 60 days with development of ARDS as a primary outcome; ARDS-related mortality and organ dysfunction were secondary outcomes.
  
  
  RESULTS
  Patients homozygous for the 4 base pair deletion in the promoter of NFKB1 (del/del) did not have an increased odds ratio (OR) of developing ARDS in unadjusted analysis but were more likely to develop ARDS in the presence of a significant interaction between the del/del genotype and age (OR 5.21, 95% CI 1.35-20.0). In multivariate analysis, patients with ARDS and the del/del genotype also had increased 60 day mortality (HR 1.54, 95% CI 1.01-2.36) and more severe daily organ dysfunction (P<.001) when compared to ARDS patients with other genotypes.
  
  
  CONCLUSIONS
  The del/del genotype is associated with an age-dependent increase in odds of developing ARDS. Patients with the del/del genotype and ARDS also have increased hazard of 60 day mortality and more organ failure.
authors.affiliation: Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ednan K
authors.initials: EK
authors.lastname: Bajwa
authors.forename: Paul C
authors.initials: PC
authors.lastname: Cremer
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Gong
authors.forename: Rihong
authors.initials: R
authors.lastname: Zhai
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012128:Respiratory Distress Syndrome / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human