4G4G genotype of the plasminogen activator inhibitor-1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia

A. Binder, G. Endler, M. Müller, C. Mannhalter, Werner Zenz*, B. Töpke, P. Fucik, J. M. Penzien, G. Diab, R. Miething, K. H. Deeg, J. Hammer, U. Heininger, V. Varnholt, A. Schmidt, L. Bindl, U. Sillaber, C. Huemer, P. Meier, G. Simic-SchleicherM. Markart, E. Pfau, H. Broede, B. Ausserer, H. Kalhoff, V. Arpe, S. Schweitzer-Krantz, J. M. Kasper, K. Loranth, H. J. Bittrich, B. Simmer, N. Weigand, E. Herting, K. H. Smolle, C. Fusch, A. Gruber, U. Schimmel, S. Knaufer-Schiefer, W. Lässig, A. Hennenberger, A. von der Wense, R. Tillmann, J. Schwarick, F. C. Sitzmann, H. Müller, P. Kurnik, P. Groneck, H. Gröblacher-Roth, J. Bensch, R. Moser, R. Schwarz, K. Lenz, T. Hofmann, W. Göpel, T. Berger, E. Hauser, K. Martin Förster, J. Peters, T. Nicolai, B. Kumlien, R. Beckmann, C. Seitz, D. Hüseman, R. Schürmann, V. H. Ta, E. Weikmann, W. Evert, J. Hautz, J. Seidenberg, L. Wocko, P. Luigs, H. L. Reiter, J. Quietzach, M. König, J. Herrmann, H. Mitter, E. Seidler, B. Maak, W. Sperl, M. Meissl, R. Koch, M. Cremer, H. A. Breuer, W. Görke, R. Nossal, W. Pernice, H. R. Salzer, H. Koch, G. Schaller, F. Paky, F. Straßer, F. Eitelberger, D. Sontheimer, A. Lischka, A. Dilch, C. Scheibenpflug, R. Bruckner, K. Runge, W. Kunze, P. Schermann

*Korrespondierende/r Autor/-in für diese Arbeit
38 Zitate (Scopus)

Abstract

Background: Meningococcal disease may present as sepsis, meningitis or a combination of both. Impaired fibrinolysis and massive elevation of the plasminogen activator inhibitor-1 (PAI-1) is a characteristic feature of meningococcal sepsis. We and others have reported an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1 gene in children with meningococcal sepsis. Objective: Multicenter study to investigate the association of the 4G/5G PAI-1 polymorphism and disseminated intravascular coagulation (DIC) in children with meningococcal disease in a Central European population. Patients/Methods: Blood samples and clinical information of 326 previously healthy children with meningococcal infection were collected from 95 pediatric hospitals in Germany, Switzerland, Italy, and Austria from 2000 to 2002. Results: DIC, defined as platelet counts below 100GL-1, increased D-dimer levels and prolonged prothrombin time, was significantly associated with the 4G4G genotype [31 of 63 (49%) vs. 55 of 175 (31%), P = 0.014], resulting in a hazard ratio (HR) of 1.5 (95% confidence interval 1.1-2.1) to develop DIC. Carriers of the 4G4G genotype showed significantly lower platelet counts (183GL-1 vs. 227GL-1, P = 0.009) on admission. Fibrinogen and C-reactive protein levels were not associated with the PAI-1 4G/5G polymorphism, nor were white blood cell counts. Conclusions: Our data show a correlation between the 4G4G genotype of the PAI-1 gene and development of DIC in meningococcal infection.

OriginalspracheEnglisch
ZeitschriftJournal of Thrombosis and Haemostasis
Jahrgang5
Ausgabenummer10
Seiten (von - bis)2049-2054
Seitenumfang6
ISSN1538-7933
DOIs
PublikationsstatusVeröffentlicht - 10.2007

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

Fingerprint

Untersuchen Sie die Forschungsthemen von „4G4G genotype of the plasminogen activator inhibitor-1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitieren