Association between urokinase haplotypes and outcome from infection-associated acute lung injury - PubMed (original) (raw)

Multicenter Study

doi: 10.1007/s00134-007-0930-6. Epub 2007 Nov 10.

Affiliations

Multicenter Study

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

John Arcaroli et al. Intensive Care Med. 2008 Feb.

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.

PubMed Disclaimer

References

    1. Crit Care Med. 2003 Apr;31(4 Suppl):S213-20 - PubMed
    1. Crit Care Med. 2006 Jun;34(6):1725-30 - PubMed
    1. Cell Mol Life Sci. 1999 Oct 1;56(1-2):104-32 - PubMed
    1. Crit Care Med. 2007 Aug;35(8):1821-8 - PubMed
    1. Clin Exp Med. 2005 Mar;4(4):202-6 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources