Bajwa, Ednan K.Cremer, Paul C.Gong, Michelle N.Zhai, RihongSu, LiThompson, B. TaylorChristiani, David C.Toland, Amanda Ewart2019-09-302011Bajwa, Ednan K., Paul C. Cremer, Michelle N. Gong, Rihong Zhai, Li Su, B. Taylor Thompson, and David C. Christiani. 2011. “An NFKB1 Promoter Insertion/Deletion Polymorphism Influences Risk and Outcome in Acute Respiratory Distress Syndrome among Caucasians.” Edited by Amanda Ewart Toland. PLoS ONE 6 (5): e19469. https://doi.org/10.1371/journal.pone.0019469.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:41426782Background: Nuclear factor-kappa B (NF-kappa B) 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.en-USJournal Article2019-09-3010.1371/journal.pone.0019469