Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent

• Published in: Intensive care medicine Vol. 33; no. 8; pp. 1354 - 1362
• Main Authors: García-Segarra, Gloria, Espinosa, Gerard, Tassies, Dolors, Oriola, Josep, Aibar, Jesús, Bové, Albert, Castro, Pedro, Reverter, Joan-Carles, Nicolás, Josep-Maria
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.08.2007; Berlin Springer Nature B.V
• Subjects: Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Blood. Blood coagulation. Reticuloendothelial system; Dimers; Epidemiology; Failure; Female; Gene polymorphism; Genotype & phenotype; Genotyping; Homozygotes; Hospital Mortality; Hospitals; Humans; Infections; Inflammation; Inflammatory response; Intensive care; Intensive care medicine; Intensive Care Units; Interleukin 1; Male; Medical Records; Medical sciences; Middle Aged; Mortality; Multiple Organ Failure - genetics; Patients; Pharmacology. Drug treatments; Physiology; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen activator inhibitors; Polymorphism; Polymorphism, Genetic; Sepsis; Septic shock; Shock, Septic - genetics; Shock, Septic - mortality; Spain; Systemic inflammatory response syndrome; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Tumor necrosis factor; Tumor necrosis factor-TNF; Whites - genetics; Spain; Shock; Human; Septic shock, Organ failure, Fibrinolysis; Intensive care; Mortality; Genotype; Polymorphisms; Fibrinolysis; Infection; Plasminogen activator inhibitor 1; Plasminogen; Caucasoid; Resuscitation; Polymorphism
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-007-0695-y

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. Prospective, observational study in a medical intensive care unit of a university hospital. 224 consecutively admitted patients. 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. The primary outcome variables were organ dysfunction and mortality. 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. 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.