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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.    Conclusion  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.

An NFKB1 Promoter Insertion/Deletion Polymorphism Influences Risk and Outcome in Acute Respiratory Distress Syndrome among Caucasians