Intensive Care Medicine

, Volume 34, Issue 2, pp 300–307

Association between urokinase haplotypes and outcome from infection-associated acute lung injury

  • John Arcaroli
  • Jeff Sankoff
  • Nianjun Liu
  • David B. Allison
  • James Maloney
  • Edward Abraham
Original

DOI: 10.1007/s00134-007-0930-6

Cite this article as:
Arcaroli, J., Sankoff, J., Liu, N. et al. Intensive Care Med (2008) 34: 300. doi:10.1007/s00134-007-0930-6
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Abstract

Objective

Alterations in coagulation, including elevated pulmonary and systemic concentrations of urokinase, are frequent in patients with acute lung injury (ALI). Urokinase potentiates neutrophil activation and contributes to the severity of pulmonary injury in preclinical models of ALI. The objective of this study was to examine associations between polymorphisms and haplotypes of urokinase with risk for and outcomes from ALI.

Design

Prospective cohorts of healthy European-American adults and those with infection-associated ALI.

Setting

Academic medical centers participating in NIH funded studies of low tidal volume ventilation for ALI.

Patients

Controls were 175 healthy European-American subjects. Patients were 252 individuals with infection-associated ALI, prospectively followed for 60 days for mortality.

Interventions

Genetic polymorphisms and haplotypes in the urokinase gene were determined.

Measurements and main results

Six polymorphisms, rs1916341, rs2227562, rs2227564, rs2227566, rs2227571, and rs4065, defining 98% of all urokinase haplotypes, were analyzed. There were no statistically significant associations between any single urokinase polymorphism or haplotype and risk for developing ALI. In contrast, there was a statistically significant relationship between the CGCCCC haplotype and both 60-day mortality and ventilator-free days that remained present in a multivariate analysis controlling for age and sex (p = 0.033 for 60-day mortality and < 0.001 for ventilator-free days).

Conclusions

These results identify a specific urokinase haplotype as a genetic risk factor for higher mortality and more severe clinical outcome in patients with infection-associated ALI.

Keywords

Acute lung injury Genetics Urokinase Sepsis Polymorphisms Haplotypes 

Supplementary material

134_2007_930_MOESM1_ESM.doc (70 kb)
Electronic Supplementary Material (DOC 70K)

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • John Arcaroli
    • 1
  • Jeff Sankoff
    • 2
  • Nianjun Liu
    • 3
  • David B. Allison
    • 3
  • James Maloney
    • 1
  • Edward Abraham
    • 4
  1. 1.Division of Pulmonary Sciences and Critical Care Medicine, Department of SurgeryUniversity of Colorado at Denver and Health Sciences CenterDenverUSA
  2. 2.Division of Emergency Medicine, Department of SurgeryUniversity of Colorado at Denver and Health Sciences CenterDenverUSA
  3. 3.Section on Statistical Genetics, Department of BiostatisticsUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Department of Medicine, Chairman’s OfficeUniversity of Alabama at BirminghamBirminghamUSA

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