4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene is associated with multiple organ dysfunction in critically ill patients

Muhammad Aminul Huq, Naoshi Takeyama, Makoto Harada, Yasuo Miki, Akinori Takeuchi, Sousuke Inoue, Takashi Nakagawa, Hideki Kanou, Akihiko Hirakawa, Hiroshi Noguchi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: Impaired fibrinolysis is associated with a higher incidence of both multiple organ dysfunction and mortality in the intensive care unit (ICU). Plasminogen activator inhibitor (PAI)-1 is the chief inhibitor of fibrinolysis. We investigated the influence of the 4G/5G polymorphism (rs1799768) of the PAI-1 gene on the plasma PAI-1 level and the outcome of critically ill patients. Methods: In 41 consecutive patients admitted to the ICU, PAI-1 gene polymorphism was assessed, plasma PAI-1 and arterial lactate concentrations were measured and clinical severity scores were recorded. Results: Homozygotes for the 4G allele had higher plasma levels of PAI-1 antigen. The mean ± SD PAI-1 antigen level was 193.31 ± 167.93 ng/ml for the 4G/4G genotype, 100.67 ± 114.16 ng/ml for the 4G/5G genotype and 0.43 ± 0.53 ng/ml for the 5G/5G genotype. There was a significant correlation between plasma PAI-1 and arterial lactate concentrations, as well as between PAI-1 and severity scores. The mortality rate was 63, 33 and 0% for patients with the 4G/4G , 4G/5G and 5G/5G genotypes, respectively. Conclusions: These results demonstrate that the 4G/5G polymorphism of the PAI-1 gene affects the plasma PAI-1 concentration, which could impair fibrinolysis and cause organ failure, and thus the presence of the 4G allele increases the risk of death.

Original languageEnglish
Pages (from-to)72-80
Number of pages9
JournalActa Haematologica
Volume127
Issue number2
DOIs
Publication statusPublished - 01-02-2012

All Science Journal Classification (ASJC) codes

  • Hematology

Fingerprint Dive into the research topics of '4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene is associated with multiple organ dysfunction in critically ill patients'. Together they form a unique fingerprint.

  • Cite this

    Huq, M. A., Takeyama, N., Harada, M., Miki, Y., Takeuchi, A., Inoue, S., Nakagawa, T., Kanou, H., Hirakawa, A., & Noguchi, H. (2012). 4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene is associated with multiple organ dysfunction in critically ill patients. Acta Haematologica, 127(2), 72-80. https://doi.org/10.1159/000333130