<i>4G/5G</i> Polymorphism of the Plasminogen Activator Inhibitor-1 Gene Is Associated with Multiple Organ Dysfunction in Critically Ill Patients

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.

Dependence of plasminogen activator inhibitor-1 level on -675 4G/5G polymorphism in PAI-1 gene in patients with traumatic brain injury

“…Одним з основних патогенетичних чинників ішемічних розладів вважають порушення процесів фібринолізу, пов'язаних з активацією плазміногену. Доведено, що інгібітор активатора плазміногену 1 типу (plasminogen activator inhibitor -PAI-1) є одним з основних компонентів фібринолітичної системи крові [6][7][8][9]. Зміни рівня PAI-1 у плазмі можуть бути зумовлені генетичними змінами, а саме -675 4G/5G поліморфізмом гена PAI-1 [6,8,10].…”