Original clinical investigation

Increased PAI-1 plasma levels and risk of death from dengue: no association with the 4G/5G promoter polymorphism

ATA Mairuhu¹ , TE Setiati² , P Koraka³ , CE Hack^4,5,6 , A Leyte⁷ , SMH Faradz⁸ , H ten Cate^9,10 , DPM Brandjes¹ , ADME Osterhaus³ , PH Reitsma¹¹ and ECM van Gorp¹

¹  Department of Internal Medicine, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands

²  Department of Paediatrics, Dr. Kariadi Hospital, Semarang, Indonesia

³  Institute of Virology, Erasmus Medical Centre, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands

⁴  Department of Immunopathology, Sanquin Research, P.O. Box 9190, 1006 AD Amsterdam, The Netherlands

⁵  Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands

⁶  Department of Clinical Chemistry, VU Medical Centre, Amsterdam, The Netherlands

⁷  Hematology and Clinical Chemistry Laboratory, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands

⁸  Molecular and Cytogenetics Unit, Biotechnology Laboratory, Medical Faculty Diponegoro University, Semarang, Indonesia

⁹  Department of Internal Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands

¹⁰  Cardiovascular Research Institute, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands

¹¹  Laboratory for Experimental Medicine, Academic Medical Centre, Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands

author email corresponding author email

Thrombosis Journal 2005, 3:17doi:10.1186/1477-9560-3-17

Published:	7 November 2005

Abstract

Background

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, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue.

Methods

A 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.

Results

Concentrations 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.

Conclusion

These 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.