The 4G/4G Genotype of PAI-1 Polymorphism Is Associated with Higher Plasma PAI-1 Concentrations and Mortality in Patients with Severe Sepsis

PLoS One. 2015 Jun 11;10(6):e0129565. doi: 10.1371/journal.pone.0129565. eCollection 2015.

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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Humans
  • Intensive Care Units
  • Logistic Models
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Genetic*
  • Prospective Studies
  • Sepsis / genetics*
  • Sepsis / mortality*
  • Spain
  • Survival Analysis

Substances

  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human

Grants and funding

This study was supported by grants from Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación y Fomento de la Investigación (SGEFI) (PI14/00220) (Madrid, Spain) and co-financed with Fondo Europeo de Desarrollo Regional (FEDER). The funders have not affected study design; the collection, analysis, and interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication.