Abstract
BackgroundDengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue.MethodsA total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis.ResultsConcentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9–23.8], peak value during admission: OR 6.3 [95%CI 1.3–30.8]). No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue.ConclusionThese data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored.
Highlights
Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations
The viruses are transmitted to humans through infected mosquitoes, and may induce clinical manifestations ranging from a mild, uncomplicated febrile illness to the more severe dengue haemorrhagic fever and dengue shock syndrome
Of 233 enrolled patients with suspected dengue haemorrhagic fever or dengue shock syndrome admitted to the paediatric intensive care unit and the paediatric ward of the Dr Kariadi Hospital, 202 (87%) were confirmed to have acute dengue, 3 (1%) were categorised as definitely not dengue and 28 (12%) as indeterminate
Summary
Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue. The viruses are transmitted to humans through infected mosquitoes, and may induce clinical manifestations ranging from a mild, uncomplicated febrile illness to the more severe dengue haemorrhagic fever and dengue shock syndrome. Increased vascular permeability is thought to be central in the pathogenesis of dengue haemorrhagic fever and dengue shock syndrome, since it results in the loss of plasma from the vascular compartment, which may give rise to shock in severe cases. Bleeding manifestations are believed to result from thrombocytopenia and thrombocytopathia, but increasing evidence suggests an important role for other abnormalities in the coagulation and fibrinolytic systems [4]
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