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

Ednan K. Bajwa, Paul C. Cremer, Michelle Ng Gong, Rihong Zhai, Li Su, B. Taylor Thompson, David C. Christiani

Research output: Contribution to journalArticle

17 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Article numbere19469
JournalPLoS One
Volume6
Issue number5
DOIs
StatePublished - 2011

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Adult Respiratory Distress Syndrome
Polymorphism
Genes
promoter regions
genetic polymorphism
Intensive care units
Transcription
Hazards
Genotype
genotype
odds ratio
Mortality
acute respiratory distress syndrome
Odds Ratio
risk reduction
case-control studies
Base Pairing
multivariate analysis
Intensive Care Units
Multivariate Analysis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

An NFKB1 promoter insertion/deletion polymorphism influences risk and outcome in acute respiratory distress syndrome among caucasians. / Bajwa, Ednan K.; Cremer, Paul C.; Gong, Michelle Ng; Zhai, Rihong; Su, Li; Thompson, B. Taylor; Christiani, David C.

In: PLoS One, Vol. 6, No. 5, e19469, 2011.

Research output: Contribution to journalArticle

Bajwa, Ednan K. ; Cremer, Paul C. ; Gong, Michelle Ng ; Zhai, Rihong ; Su, Li ; Thompson, B. Taylor ; Christiani, David C. / An NFKB1 promoter insertion/deletion polymorphism influences risk and outcome in acute respiratory distress syndrome among caucasians. In: PLoS One. 2011 ; Vol. 6, No. 5.
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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. 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.",
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