title: 4G/5G polymorphism of plasminogen activator inhibitor-1 gene is associated with mortality in intensive care unit patients with severe pneumonia.
abstract: BACKGROUND
  Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia.
  
  
  METHODS
  The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination.
  
  
  RESULTS
  A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype.
  
  
  CONCLUSIONS
  The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia.
authors.affiliation: Department of Pediatrics, Division of Critical Care Medicine, University of California San Francisco, San Francisco, CA 94143, USA. anil.sapru@ucsf.edu
authors.forename: Anil
authors.initials: A
authors.lastname: Sapru
authors.forename: Helen
authors.initials: H
authors.lastname: Hansen
authors.forename: Temitayo
authors.initials: T
authors.lastname: Ajayi
authors.forename: Ron
authors.initials: R
authors.lastname: Brown
authors.forename: Oscar
authors.initials: O
authors.lastname: Garcia
authors.forename: HanJing
authors.initials: H
authors.lastname: Zhuo
authors.forename: Joseph
authors.initials: J
authors.lastname: Wiemels
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: Jeanine
authors.initials: J
authors.lastname: Wiener-Kronish
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004251:DNA Transposable Elements / Q000235:genetics; D005260:Female; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007362:Intensive Care Units / Q000639:trends; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011014:Pneumonia / Q000235:genetics* / Q000401:mortality*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D004251:DNA Transposable Elements; D017395:Plasminogen Activator Inhibitor 1