title: Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent.
abstract: OBJECTIVE
  To evaluate the effect of the 4G/5G PAI-1 gene polymorphism on the development of organ failure and outcome in critically ill patients with septic syndromes.
  
  
  METHODS
  Prospective, observational study in a medical intensive care unit of a university hospital.
  
  
  METHODS
  224 consecutively admitted patients.
  
  
  METHODS
  Epidemiological data, severity scores, and the primary site of infection were recorded. DNA genotyping of the PAI-1, TNF-beta, and IL1-ra genes, and measurement of plasma PAI-1 antigen and D-dimer were carried out.
  
  
  METHODS
  The primary outcome variables were organ dysfunction and mortality.
  
  
  RESULTS
  Eighty-eight subjects had septic shock at ICU entry or within 48 h from admission. Homozygotes for the 4G allele exhibited higher plasma concentrations of PAI-1 antigen and D-dimer than 4G/5G and 5G/5G subjects). ICU mortality was 44.0% in patients with 4G/4G, 23.4% in 4G/5G and 12.5% in 5G/5G, mainly due to multiorgan failure. After adjusting for SAPS II at admission the genotypes independently associated with ICU mortality in septic shock were TNF-B2/B2 (OR 2.83, 1.04-7.67) and 4G/4G of PAI-1 (OR 2.23, 1.02-4.85). The PAI-1 genotype did not determine susceptibility to infection or the outcome in nonseptic systemic inflammatory response syndrome, sepsis, severe sepsis, and nosocomial septic shock.
  
  
  CONCLUSIONS
  Homozygosity for 4G of the PAI-1 gene confers an increase in the risk of mortality in adult patients with septic shock due to a greater organ failure.
authors.affiliation: Medical Intensive Care Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: García-Segarra
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Dolors
authors.initials: D
authors.lastname: Tassies
authors.forename: Josep
authors.initials: J
authors.lastname: Oriola
authors.forename: Jesús
authors.initials: J
authors.lastname: Aibar
authors.forename: Albert
authors.initials: A
authors.lastname: Bové
authors.forename: Pedro
authors.initials: P
authors.lastname: Castro
authors.forename: Joan-Carles
authors.initials: JC
authors.lastname: Reverter
authors.forename: Josep-Maria
authors.initials: JM
authors.lastname: Nicolás
mesh_terms: D000368:Aged; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D012772:Shock, Septic / Q000235:genetics / Q000401:mortality*; D013030:Spain; D044465:White People / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1