Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent.
OBJECTIVE
To evaluate the effect of the 4G/5G PAI-1 gene polymorphism on the development of organ failure and outcome in critically ill patients with septic syndromes.


METHODS
Prospective, observational study in a medical intensive care unit of a university hospital.


METHODS
224 consecutively admitted patients.


METHODS
Epidemiological data, severity scores, and the primary site of infection were recorded. DNA genotyping of the PAI-1, TNF-beta, and IL1-ra genes, and measurement of plasma PAI-1 antigen and D-dimer were carried out.


METHODS
The primary outcome variables were organ dysfunction and mortality.


RESULTS
Eighty-eight subjects had septic shock at ICU entry or within 48 h from admission. Homozygotes for the 4G allele exhibited higher plasma concentrations of PAI-1 antigen and D-dimer than 4G/5G and 5G/5G subjects). ICU mortality was 44.0% in patients with 4G/4G, 23.4% in 4G/5G and 12.5% in 5G/5G, mainly due to multiorgan failure. After adjusting for SAPS II at admission the genotypes independently associated with ICU mortality in septic shock were TNF-B2/B2 (OR 2.83, 1.04-7.67) and 4G/4G of PAI-1 (OR 2.23, 1.02-4.85). The PAI-1 genotype did not determine susceptibility to infection or the outcome in nonseptic systemic inflammatory response syndrome, sepsis, severe sepsis, and nosocomial septic shock.


CONCLUSIONS
Homozygosity for 4G of the PAI-1 gene confers an increase in the risk of mortality in adult patients with septic shock due to a greater organ failure.
García-Segarra
Gloria
G
Medical Intensive Care Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain.
Espinosa
Gerard
G
Tassies
Dolors
D
Oriola
Josep
J
Aibar
Jesús
J
Bové
Albert
A
Castro
Pedro
P
Reverter
Joan-Carles
JC
Nicolás
Josep-Maria
JM
D000368:Aged; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D012772:Shock, Septic / Q000235:genetics / Q000401:mortality*; D013030:Spain; D044465:White People / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1