4G/5G polymorphism of plasminogen activator inhibitor-1 gene is associated with mortality in intensive care unit patients with severe pneumonia.
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.
Sapru
Anil
A
Department of Pediatrics, Division of Critical Care Medicine, University of California San Francisco, San Francisco, CA 94143, USA. anil.sapru@ucsf.edu
Hansen
Helen
H
Ajayi
Temitayo
T
Brown
Ron
R
Garcia
Oscar
O
Zhuo
HanJing
H
Wiemels
Joseph
J
Matthay
Michael A
MA
Wiener-Kronish
Jeanine
J
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
D004251:DNA Transposable Elements; D017395:Plasminogen Activator Inhibitor 1