An NFKB1 promoter insertion/deletion polymorphism influences risk and outcome in acute respiratory distress syndrome among Caucasians

• Published in: PloS one 2011-05, Vol.6 (5), p.e19469-e19469
• Main Authors: Bajwa, Ednan K, Cremer, Paul C, Gong, Michelle N, Zhai, Rihong, Su, Li, Thompson, B Taylor, Christiani, David C
• Format: Article
• Language: English
• Subjects: Adult respiratory distress syndrome; Age; Aged; Aged, 80 and over; Biology; Case-Control Studies; Centenarians; Control methods; Critical care; Cytokines; Deoxyribonucleic acid; Diabetes; Disease susceptibility; DNA; E coli; Enrollments; Environmental health; Escherichia coli; European Continental Ancestry Group - genetics; Female; Gene deletion; Gene expression; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease - genetics; Genotype; Genotypes; Health aspects; Hospitals; Humans; Inflammation; Insertion; Male; Medical research; Medical schools; Medicine; Middle Aged; Mortality; Multivariate analysis; NF-kappa B p50 Subunit - genetics; NF-κB protein; Oldest old people; Pathogenesis; Patients; Pneumonia; Polymorphism; Polymorphism, Genetic - genetics; Population; Proteins; Public health; Respiratory distress syndrome; Respiratory Distress Syndrome, Adult - epidemiology; Respiratory Distress Syndrome, Adult - genetics; Risk analysis; Risk factors; Risk management; Sepsis; Transcription; Transcription (Genetics); Trauma; Trends
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0019469

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. 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. 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