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-Schleicher; M. 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

doi:10.1111/j.1538-7836.2007.02724.x

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

Department of Pediatric Medicine

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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.

Original language	English
Pages (from-to)	2049-2054
Number of pages	6
Journal	Journal of Thrombosis and Haemostasis
Volume	5
Issue number	10
DOIs	https://doi.org/10.1111/j.1538-7836.2007.02724.x
State	Published - Oct 2007

Keywords

Disseminated intravascular coagulation
Fibrinogen
Meningococcal disease
PAI-1
Platelet count
Polymorphism

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10.1111/j.1538-7836.2007.02724.x

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Binder, A., Endler, G., Müller, M., Mannhalter, C., Zenz, W., Töpke, B., Fucik, P., Penzien, J. M., Diab, G., Miething, R., Deeg, K. H., Hammer, J., Heininger, U., Varnholt, V., Schmidt, A., Bindl, L., Sillaber, U., Huemer, C., Meier, P., ... Schermann, P. (2007). 4G4G genotype of the plasminogen activator inhibitor-1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia. Journal of Thrombosis and Haemostasis, 5(10), 2049-2054. https://doi.org/10.1111/j.1538-7836.2007.02724.x

@article{2cad0bc4f837479e8f651d5f3c2d7d0b,

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

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.",

keywords = "Disseminated intravascular coagulation, Fibrinogen, Meningococcal disease, PAI-1, Platelet count, Polymorphism",

author = "A. Binder and G. Endler and M. M{\"u}ller and C. Mannhalter and Werner Zenz and B. T{\"o}pke and P. Fucik and Penzien, {J. M.} and G. Diab and R. Miething and Deeg, {K. H.} and J. Hammer and U. Heininger and V. Varnholt and A. Schmidt and L. Bindl and U. Sillaber and C. Huemer and P. Meier and G. Simic-Schleicher and M. Markart and E. Pfau and H. Broede and B. Ausserer and H. Kalhoff and V. Arpe and S. Schweitzer-Krantz and Kasper, {J. M.} and K. Loranth and Bittrich, {H. J.} and B. Simmer and N. Weigand and E. Herting and Smolle, {K. H.} and C. Fusch and A. Gruber and U. Schimmel and S. Knaufer-Schiefer and W. L{\"a}ssig and A. Hennenberger and {von der Wense}, A. and R. Tillmann and J. Schwarick and Sitzmann, {F. C.} and H. M{\"u}ller and P. Kurnik and P. Groneck and H. Gr{\"o}blacher-Roth and J. Bensch and R. Moser and R. Schwarz and K. Lenz and T. Hofmann and W. G{\"o}pel and T. Berger and E. Hauser and F{\"o}rster, {K. Martin} and J. Peters and T. Nicolai and B. Kumlien and R. Beckmann and C. Seitz and D. H{\"u}seman and R. Sch{\"u}rmann and Ta, {V. H.} and E. Weikmann and W. Evert and J. Hautz and J. Seidenberg and L. Wocko and P. Luigs and Reiter, {H. L.} and J. Quietzach and M. K{\"o}nig and J. Herrmann and H. Mitter and E. Seidler and B. Maak and W. Sperl and M. Meissl and R. Koch and M. Cremer and Breuer, {H. A.} and W. G{\"o}rke and R. Nossal and W. Pernice and Salzer, {H. R.} and H. Koch and G. Schaller and F. Paky and F. Stra{\ss}er and F. Eitelberger and D. Sontheimer and A. Lischka and A. Dilch and C. Scheibenpflug and R. Bruckner and K. Runge and W. Kunze and P. Schermann",

year = "2007",

month = oct,

doi = "10.1111/j.1538-7836.2007.02724.x",

language = "English",

volume = "5",

pages = "2049--2054",

journal = "Journal of Thrombosis and Haemostasis",

issn = "1538-7933",

publisher = "Elsevier B.V.",

number = "10",

}

Binder, A, Endler, G, Müller, M, Mannhalter, C, Zenz, W, Töpke, B, Fucik, P, Penzien, JM, Diab, G, Miething, R, Deeg, KH, Hammer, J, Heininger, U, Varnholt, V, Schmidt, A, Bindl, L, Sillaber, U, Huemer, C, Meier, P, Simic-Schleicher, G, Markart, M, Pfau, E, Broede, H, Ausserer, B, Kalhoff, H, Arpe, V, Schweitzer-Krantz, S, Kasper, JM, Loranth, K, Bittrich, HJ, Simmer, B, Weigand, N, Herting, E, Smolle, KH, Fusch, C, Gruber, A, Schimmel, U, Knaufer-Schiefer, S, Lässig, W, Hennenberger, A, von der Wense, A, Tillmann, R, Schwarick, J, Sitzmann, FC, Müller, H, Kurnik, P, Groneck, P, Gröblacher-Roth, H, Bensch, J, Moser, R, Schwarz, R, Lenz, K, Hofmann, T, Göpel, W, Berger, T, Hauser, E, Förster, KM, Peters, J, Nicolai, T, Kumlien, B, Beckmann, R, Seitz, C, Hüseman, D, Schürmann, R, Ta, VH, Weikmann, E, Evert, W, Hautz, J, Seidenberg, J, Wocko, L, Luigs, P, Reiter, HL, Quietzach, J, König, M, Herrmann, J, Mitter, H, Seidler, E, Maak, B, Sperl, W, Meissl, M, Koch, R, Cremer, M, Breuer, HA, Görke, W, Nossal, R, Pernice, W, Salzer, HR, Koch, H, Schaller, G, Paky, F, Straßer, F, Eitelberger, F, Sontheimer, D, Lischka, A, Dilch, A, Scheibenpflug, C, Bruckner, R, Runge, K, Kunze, W & Schermann, P 2007, '4G4G genotype of the plasminogen activator inhibitor-1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia', Journal of Thrombosis and Haemostasis, vol. 5, no. 10, pp. 2049-2054. https://doi.org/10.1111/j.1538-7836.2007.02724.x

TY - JOUR

T1 - 4G4G genotype of the plasminogen activator inhibitor-1 promoter polymorphism associates with disseminated intravascular coagulation in children with systemic meningococcemia

AU - Binder, A.

AU - Endler, G.

AU - Müller, M.

AU - Mannhalter, C.

AU - Zenz, Werner

AU - Töpke, B.

AU - Fucik, P.

AU - Penzien, J. M.

AU - Diab, G.

AU - Miething, R.

AU - Deeg, K. H.

AU - Hammer, J.

AU - Heininger, U.

AU - Varnholt, V.

AU - Schmidt, A.

AU - Bindl, L.

AU - Sillaber, U.

AU - Huemer, C.

AU - Meier, P.

AU - Simic-Schleicher, G.

AU - Markart, M.

AU - Pfau, E.

AU - Broede, H.

AU - Ausserer, B.

AU - Kalhoff, H.

AU - Arpe, V.

AU - Schweitzer-Krantz, S.

AU - Kasper, J. M.

AU - Loranth, K.

AU - Bittrich, H. J.

AU - Simmer, B.

AU - Weigand, N.

AU - Herting, E.

AU - Smolle, K. H.

AU - Fusch, C.

AU - Gruber, A.

AU - Schimmel, U.

AU - Knaufer-Schiefer, S.

AU - Lässig, W.

AU - Hennenberger, A.

AU - von der Wense, A.

AU - Tillmann, R.

AU - Schwarick, J.

AU - Sitzmann, F. C.

AU - Müller, H.

AU - Kurnik, P.

AU - Groneck, P.

AU - Gröblacher-Roth, H.

AU - Bensch, J.

AU - Moser, R.

AU - Schwarz, R.

AU - Lenz, K.

AU - Hofmann, T.

AU - Göpel, W.

AU - Berger, T.

AU - Hauser, E.

AU - Förster, K. Martin

AU - Peters, J.

AU - Nicolai, T.

AU - Kumlien, B.

AU - Beckmann, R.

AU - Seitz, C.

AU - Hüseman, D.

AU - Schürmann, R.

AU - Ta, V. H.

AU - Weikmann, E.

AU - Evert, W.

AU - Hautz, J.

AU - Seidenberg, J.

AU - Wocko, L.

AU - Luigs, P.

AU - Reiter, H. L.

AU - Quietzach, J.

AU - König, M.

AU - Herrmann, J.

AU - Mitter, H.

AU - Seidler, E.

AU - Maak, B.

AU - Sperl, W.

AU - Meissl, M.

AU - Koch, R.

AU - Cremer, M.

AU - Breuer, H. A.

AU - Görke, W.

AU - Nossal, R.

AU - Pernice, W.

AU - Salzer, H. R.

AU - Koch, H.

AU - Schaller, G.

AU - Paky, F.

AU - Straßer, F.

AU - Eitelberger, F.

AU - Sontheimer, D.

AU - Lischka, A.

AU - Dilch, A.

AU - Scheibenpflug, C.

AU - Bruckner, R.

AU - Runge, K.

AU - Kunze, W.

AU - Schermann, P.

PY - 2007/10

Y1 - 2007/10

N2 - 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.

AB - 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.

KW - Disseminated intravascular coagulation

KW - Fibrinogen

KW - Meningococcal disease

KW - PAI-1

KW - Platelet count

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=34548839906&partnerID=8YFLogxK

U2 - 10.1111/j.1538-7836.2007.02724.x

DO - 10.1111/j.1538-7836.2007.02724.x

M3 - Article

C2 - 17697137

AN - SCOPUS:34548839906

SN - 1538-7933

VL - 5

SP - 2049

EP - 2054

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

IS - 10

ER -

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

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