title: 4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene is associated with multiple organ dysfunction in critically ill patients.
abstract: OBJECTIVE
  Impaired fibrinolysis is associated with a higher incidence of both multiple organ dysfunction and mortality in the intensive care unit (ICU). Plasminogen activator inhibitor (PAI)-1 is the chief inhibitor of fibrinolysis. We investigated the influence of the 4G/5G polymorphism (rs1799768) of the PAI-1 gene on the plasma PAI-1 level and the outcome of critically ill patients.
  
  
  METHODS
  In 41 consecutive patients admitted to the ICU, PAI-1 gene polymorphism was assessed, plasma PAI-1 and arterial lactate concentrations were measured and clinical severity scores were recorded.
  
  
  RESULTS
  Homozygotes for the 4G allele had higher plasma levels of PAI-1 antigen. The mean ± SD PAI-1 antigen level was 193.31 ± 167.93 ng/ml for the 4G/4G genotype, 100.67 ± 114.16 ng/ml for the 4G/5G genotype and 0.43 ± 0.53 ng/ml for the 5G/5G genotype. There was a significant correlation between plasma PAI-1 and arterial lactate concentrations, as well as between PAI-1 and severity scores. The mortality rate was 63, 33 and 0% for patients with the 4G/4G, 4G/5G and 5G/5G genotypes, respectively.
  
  
  CONCLUSIONS
  These results demonstrate that the 4G/5G polymorphism of the PAI-1 gene affects the plasma PAI-1 concentration, which could impair fibrinolysis and cause organ failure, and thus the presence of the 4G allele increases the risk of death.
authors: Department of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, Japan.
authors: Muhammad Aminul
authors: MA
authors: Huq
authors: Naoshi
authors: N
authors: Takeyama
authors: Makoto
authors: M
authors: Harada
authors: Yasuo
authors: Y
authors: Miki
authors: Akinori
authors: A
authors: Takeuchi
authors: Sousuke
authors: S
authors: Inoue
authors: Takashi
authors: T
authors: Nakagawa
authors: Hideki
authors: H
authors: Kanou
authors: Akihiko
authors: A
authors: Hirakawa
authors: Hiroshi
authors: H
authors: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000235:genetics* / Q000401:mortality; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D019344:Lactic Acid