Role of 4G/5G plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and the PAI-1 plasma levels in the outcome of patients with severe sepsis

Introduction

The objective of this study was to evaluate the effect of the 4G/5G plasminogen activator inhibitor-1 (PAI-1) gene polymorphism on the plasma PAI-1 levels and outcome in critically ill patients with severe sepsis.

Methods

A prospective, observational and multicenter study carried out in six Spanish ICUs. Only patients with severe sepsis were included. Epidemiological data, severity scores, site of infection and outcome of sepsis were recorded. Measurement of PAI-1 plasma levels (at diagnosis, 72 hours and 7 days of diagnosis of severe sepsis) and the DNA genotyping of the PAI-1 were carried out.

Results

A total of 122 patients with severe sepsis were included. Nonsurvivor patients (n = 53) exhibited higher PAI-1 plasma concentrations than the survivor patients (n = 69) at the time of diagnosis of severe sepsis (60.17 ± 30.34 vs. 42.51 ± 28.85; P = 0.001), at 72 hours (34.74 ± 20.79 vs. 17.91 ± 12.85; P ≤ 0.001), and at 7 days (35.93 ± 21.16 vs. 24.77 ± 15.85; P = 0.07). PAI-1 plasma levels at diagnosis were found a predictor of mortality (OR = 1.02, 95% CI = 1.01 to 1.03, P = 0.001). We did not find significant differences between 4G/5G PAI-1 gene polymorphisms in the PAI-1 plasma levels (49.20 ± 26.15 with 4G/4G genotype, 49.39 ± 30.63 with 4G/5G genotype, and 48.06 ± 32.26 with 5G/5G genotype), and in the mortality (10/23 (41%) with 4G/4G genotype, 25/60 (40%) with 4G/5G and 18/39 (47%) with 5G/5G).

Conclusion

PAI-1 plasma levels at the time of diagnosis are markers of an unfavourable prognosis in patients with severe sepsis. We have not, however, found any correlation between the 4G/5G PAI-1 gene polymorphism, plasma levels of PAI-1 or mortality of patients with severe sepsis.