title: The 4G/4G Genotype of PAI-1 Polymorphism Is Associated with Higher Plasma PAI-1 Concentrations and Mortality in Patients with Severe Sepsis.
abstract: OBJECTIVE
  Two studies have reported that patients with the 4G/4G genotype of the plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism had higher plasma PAI-1 concentrations and higher risk of death than those with the 4G/5G or 5G/5G genotypes; one study involved 175 children with meningococcal disease, and the other included 88 adult patients with septic shock. Thus, the objective of this study was to determine whether there is an association between carriage of the 4G/4G genotype, plasma PAI-1 concentrations and mortality in a large series of adult septic patients.
  
  
  METHODS
  An observational, prospective, multicenter study was carried out in six Spanish Intensive Care Units including severe septic patients. We determined the PAI-1 4G/5G polymorphism and plasma PAI-1 concentrations in all patients. The end-points of the study were 30-day and 6-month mortality.
  
  
  RESULTS
  We included a total of 260 patients, 82 (31.5%) with 4G/4G, 126 (48.5%) with 4G/5G and 52 (20.0%) with 5G/5G genotype. Multivariate logistic regression analysis showed that the 4G/4G genotype was associated with higher mortality at 30 days (Odds Ratio = 1.95; 95% CI = 1.063-3.561; p = 0.03) and at 6 months (Odds Ratio = 2.19; 95% CI = 1.221-3.934; p = 0.01), and that higher plasma PAI-1 concentrations were associated with higher mortality at 30 days (Odds Ratio = 1.01; 95% CI = 1.002-1.022; p = 0.02) at 6 months (Odds Ratio = 1.01; 95% CI = 1.003-1.023; p = 0.01). Multivariate linear regression analysis showed that increased plasma PAI-1 concentrations were associated with the PAI-1 4G/4G genotype (regression coefficient = 4.82; 95% CI = 3.227 to 6.406; p<0.001).
  
  
  CONCLUSIONS
  The major findings of our study, to our knowledge the largest series reporting data about 4G/5G polymorphism of the PAI-1 gene, plasma PAI-1 concentrations and mortality in septic patients, were that septic patients with the 4G/4G genotype had higher plasma PAI-1 concentrations and higher risk of death than those with 4G/5G or 5G/5G genotypes.
authors.affiliation: Intensive Care Unit, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lorente
authors.affiliation: Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Santa Cruz Tenerife, Spain.
authors.forename: María M
authors.initials: MM
authors.lastname: Martín
authors.affiliation: Laboratory Deparment, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Borreguero-León
authors.affiliation: Laboratory Deparment of the Research Unit, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain.
authors.forename: Ysamar
authors.initials: Y
authors.lastname: Barrios
authors.affiliation: Intensive Care Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.affiliation: Intensive Care Unit, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Ferreres
authors.affiliation: Intensive Care Unit, Hospital San Jorge, Huesca, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Labarta
authors.affiliation: Intensive Care Unit, Hospital Insular, Las Palmas de Gran Canaria, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Díaz
authors.affiliation: Statistical Deparment of the Research Unit, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018805:Sepsis / Q000235:genetics* / Q000401:mortality*; D013030:Spain; D016019:Survival Analysis
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human