The impact of the PAI-1 4G/5G polymorphism on the outcome of patients with ALI/ARDS.
BACKGROUND
Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS.


METHODS
52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days.


RESULTS
17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p=0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio=9.95, 95% CI: 1.79-55.28, p=0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p=0.033 and p=0.008, respectively).


CONCLUSIONS
ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure.
Tsangaris
Iraklis
I
2nd Department of Critical Care Medicine, Attikon Hospital, Medical School, University of Athens, Athens, Greece. itsagkaris@med.uoa.gr
Tsantes
Argiris
A
Bonovas
Stefanos
S
Lignos
Michalis
M
Kopterides
Petros
P
Gialeraki
Argiro
A
Rapti
Evdoxia
E
Orfanos
Stylianos
S
Dimopoulou
Ioanna
I
Travlou
Anthi
A
Armaganidis
Apostolos
A
D055371:Acute Lung Injury / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000628:therapy
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human