4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia

Gotho Geishofer; Alexander Binder; Martin Müller; Bettina Zöhrer; Bernhard Resch; Wilhelm Müller; Jörg Faber; Adam Finn; Georg Endler; Christine Mannhalter; Werner Zenz; Bärbel Töpke; Peter Fucik; Johann M. Penzien; Gedeon Diab; Robert Miething; K. H. Deeg; Jürg Hammer; Ulrich Heininger; Verena Varnholt; Andreas Schmidt; Lutz Bindl; Ursula Sillaber; Christian Huemer; Primrose Meier; G. Simic-Schleicher; Markus Markart; Eberhard Pfau; Hans Broede; Bernd Ausserer; Hermann Kalhoff; Volker Arpe; Susanne Schweitzer-Krantz; Johannes Martin Kasper; Kathrin Loranth; Hans J. Bittrich; Burkhard Simmer; Nicola Weigand; Egbert Herting; Karl Heinz Smolle; Christoph Fusch; Alois Gruber; Ulf Schimmel; Suzanne Knaufer-Schiefer; Wolfgang Lässig; Axel Hennenberger; Axel Von Der Wense; Roland Tillmann; Jürgen Schwarick; F. C. Sitzmann; Herbert Müller; Peter Kurnik; Peter Groneck; Helene Gröblacher-Roth; Jürgen Bensch; Reinhard Moser; Rudolf Schwarz; Kurt Lenz; Thomas Hofmann; Wolfgang Göpel; Thomas Berger; Erwin Hauser; Kai Martin Förster; Jochen Peters; Thomas Nicolai; Björn Kumlien; Regina Beckmann; Christiane Seitz; D. Hüseman; Roland Schürmann; Van Hop Ta; Eckart Weikmann; W. Evert; Jürgen Hautz; Jürgen Seidenberg; Lucia Wocko; Petra Luigs; Hans Ludwig Reiter; J. Quietzach; Michael König; Johanna Herrmann; Horst Mitter; Ekkehard Seidler; Bernhard Maak; Wolfgang Sperl; Manfred Meissl; Reinhard Koch; Manfred Cremer; H. A. Breuer; W. Görke; Robert Nossal; Walter Pernice; Hans R. Salzer; Hartmut Koch; Gerhard Schaller; Franz Paky; Friedrich Straßer; Franz Eitelberger; D. Sontheimer; Andreas Lischka; Alfred Dilch; Christian Scheibenpflug; Robert Bruckner; Klaus Runge; Wolfgang Kunze; Peter Schermann

doi:10.1007/s00431-005-1673-4

4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia

Gotho Geishofer, Alexander Binder, Martin Müller, Bettina Zöhrer, Bernhard Resch, Wilhelm Müller, Jörg Faber, Adam Finn, Georg Endler, Christine Mannhalter, Werner Zenz^*, Bärbel Töpke, Peter Fucik, Johann M. Penzien, Gedeon Diab, Robert Miething, K. H. Deeg, Jürg Hammer, Ulrich Heininger, Verena VarnholtAndreas Schmidt, Lutz Bindl, Ursula Sillaber, Christian Huemer, Primrose Meier, G. Simic-Schleicher, Markus Markart, Eberhard Pfau, Hans Broede, Bernd Ausserer, Hermann Kalhoff, Volker Arpe, Susanne Schweitzer-Krantz, Johannes Martin Kasper, Kathrin Loranth, Hans J. Bittrich, Burkhard Simmer, Nicola Weigand, Egbert Herting, Karl Heinz Smolle, Christoph Fusch, Alois Gruber, Ulf Schimmel, Suzanne Knaufer-Schiefer, Wolfgang Lässig, Axel Hennenberger, Axel Von Der Wense, Roland Tillmann, Jürgen Schwarick, F. C. Sitzmann, Herbert Müller, Peter Kurnik, Peter Groneck, Helene Gröblacher-Roth, Jürgen Bensch, Reinhard Moser, Rudolf Schwarz, Kurt Lenz, Thomas Hofmann, Wolfgang Göpel, Thomas Berger, Erwin Hauser, Kai Martin Förster, Jochen Peters, Thomas Nicolai, Björn Kumlien, Regina Beckmann, Christiane Seitz, D. Hüseman, Roland Schürmann, Van Hop Ta, Eckart Weikmann, W. Evert, Jürgen Hautz, Jürgen Seidenberg, Lucia Wocko, Petra Luigs, Hans Ludwig Reiter, J. Quietzach, Michael König, Johanna Herrmann, Horst Mitter, Ekkehard Seidler, Bernhard Maak, Wolfgang Sperl, Manfred Meissl, Reinhard Koch, Manfred Cremer, H. A. Breuer, W. Görke, Robert Nossal, Walter Pernice, Hans R. Salzer, Hartmut Koch, Gerhard Schaller, Franz Paky, Friedrich Straßer, Franz Eitelberger, D. Sontheimer, Andreas Lischka, Alfred Dilch, Christian Scheibenpflug, Robert Bruckner, Klaus Runge, Wolfgang Kunze, Peter Schermann

^*Corresponding author for this work

Clinic of Pediatric and Adolescent Medicine

59 Citations (Scopus)

Abstract

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. Previously, an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1gene in a cohort of UK and Dutch children with meningococcal sepsis was reported. We carried out a prospective, multicentre study to investigate the association of the 4G/5G PAI-1 polymorphism, diagnosis, and outcome in meningococcal disease in a Central European and UK population. Blood samples and clinical information of 347 previously healthy children with meningococcal infection were collected from 95 paediatric hospitals in Germany, Switzerland, Italy, the United Kingdom, and Austria from 2000 until 2002. Mortality was significantly associated with the 4G/4G genotype (12 of 90 (13%) vs. 15 of 240 (6%), P =0.037), resulting in an odds ratio of 2.31. The diagnosis of sepsis (independent of symptoms of meningitis) was significantly more frequent in carriers of the 4G/4G genotype (P =0.01), resulting in an odds ratio of 2.21 to develop sepsis. Meningitis was not associated with the PAI-1 4G/5G polymorphism, and allele frequencies were similar in patient and control groups. Conclusion:Our data show a correlation between the 4G/4G genotype in the plasminogen activator inhibitor-1 gene and poor outcome in children with meningococcal infection. In addition, 4G homozygous patients were prone to develop sepsis. We found no influence of the plasminogen activator inhibitor-1 polymorphism on the susceptibility to invasive meningococcal infection.

Original language	English
Journal	European Journal of Pediatrics
Volume	164
Issue number	8
Pages (from-to)	486-490
Number of pages	5
ISSN	0340-6199
DOIs	https://doi.org/10.1007/s00431-005-1673-4
Publication status	Published - 07.2005

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Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00431-005-1673-4

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Geishofer, G., Binder, A., Müller, M., Zöhrer, B., Resch, B., Müller, W., Faber, J., Finn, A., Endler, G., Mannhalter, C., Zenz, W., Töpke, B., Fucik, P., Penzien, J. M., Diab, G., Miething, R., Deeg, K. H., Hammer, J., Heininger, U., ... Schermann, P. (2005). 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia. European Journal of Pediatrics, 164(8), 486-490. https://doi.org/10.1007/s00431-005-1673-4

@article{75838989528f407787ff8777b80c90e5,

title = "4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia",

abstract = "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. Previously, an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1gene in a cohort of UK and Dutch children with meningococcal sepsis was reported. We carried out a prospective, multicentre study to investigate the association of the 4G/5G PAI-1 polymorphism, diagnosis, and outcome in meningococcal disease in a Central European and UK population. Blood samples and clinical information of 347 previously healthy children with meningococcal infection were collected from 95 paediatric hospitals in Germany, Switzerland, Italy, the United Kingdom, and Austria from 2000 until 2002. Mortality was significantly associated with the 4G/4G genotype (12 of 90 (13%) vs. 15 of 240 (6%), P =0.037), resulting in an odds ratio of 2.31. The diagnosis of sepsis (independent of symptoms of meningitis) was significantly more frequent in carriers of the 4G/4G genotype (P =0.01), resulting in an odds ratio of 2.21 to develop sepsis. Meningitis was not associated with the PAI-1 4G/5G polymorphism, and allele frequencies were similar in patient and control groups. Conclusion:Our data show a correlation between the 4G/4G genotype in the plasminogen activator inhibitor-1 gene and poor outcome in children with meningococcal infection. In addition, 4G homozygous patients were prone to develop sepsis. We found no influence of the plasminogen activator inhibitor-1 polymorphism on the susceptibility to invasive meningococcal infection.",

author = "Gotho Geishofer and Alexander Binder and Martin M{\"u}ller and Bettina Z{\"o}hrer and Bernhard Resch and Wilhelm M{\"u}ller and J{\"o}rg Faber and Adam Finn and Georg Endler and Christine Mannhalter and Werner Zenz and B{\"a}rbel T{\"o}pke and Peter Fucik and Penzien, {Johann M.} and Gedeon Diab and Robert Miething and Deeg, {K. H.} and J{\"u}rg Hammer and Ulrich Heininger and Verena Varnholt and Andreas Schmidt and Lutz Bindl and Ursula Sillaber and Christian Huemer and Primrose Meier and G. Simic-Schleicher and Markus Markart and Eberhard Pfau and Hans Broede and Bernd Ausserer and Hermann Kalhoff and Volker Arpe and Susanne Schweitzer-Krantz and Kasper, {Johannes Martin} and Kathrin Loranth and Bittrich, {Hans J.} and Burkhard Simmer and Nicola Weigand and Egbert Herting and Smolle, {Karl Heinz} and Christoph Fusch and Alois Gruber and Ulf Schimmel and Suzanne Knaufer-Schiefer and Wolfgang L{\"a}ssig and Axel Hennenberger and {Von Der Wense}, Axel and Roland Tillmann and J{\"u}rgen Schwarick and Sitzmann, {F. C.} and Herbert M{\"u}ller and Peter Kurnik and Peter Groneck and Helene Gr{\"o}blacher-Roth and J{\"u}rgen Bensch and Reinhard Moser and Rudolf Schwarz and Kurt Lenz and Thomas Hofmann and Wolfgang G{\"o}pel and Thomas Berger and Erwin Hauser and F{\"o}rster, {Kai Martin} and Jochen Peters and Thomas Nicolai and Bj{\"o}rn Kumlien and Regina Beckmann and Christiane Seitz and D. H{\"u}seman and Roland Sch{\"u}rmann and Ta, {Van Hop} and Eckart Weikmann and W. Evert and J{\"u}rgen Hautz and J{\"u}rgen Seidenberg and Lucia Wocko and Petra Luigs and Reiter, {Hans Ludwig} and J. Quietzach and Michael K{\"o}nig and Johanna Herrmann and Horst Mitter and Ekkehard Seidler and Bernhard Maak and Wolfgang Sperl and Manfred Meissl and Reinhard Koch and Manfred Cremer and Breuer, {H. A.} and W. G{\"o}rke and Robert Nossal and Walter Pernice and Salzer, {Hans R.} and Hartmut Koch and Gerhard Schaller and Franz Paky and Friedrich Stra{\ss}er and Franz Eitelberger and D. Sontheimer and Andreas Lischka and Alfred Dilch and Christian Scheibenpflug and Robert Bruckner and Klaus Runge and Wolfgang Kunze and Peter Schermann",

note = "Funding Information: Acknowledgements This study was supported by the Jubil{\"a}umsfond der {\"O}sterreichischen Nationalbank, grants 8842 and 10112. Copyright: Copyright 2013 Elsevier B.V., All rights reserved.",

year = "2005",

month = jul,

doi = "10.1007/s00431-005-1673-4",

language = "English",

volume = "164",

pages = "486--490",

journal = "European Journal of Pediatrics",

issn = "0340-6199",

number = "8",

}

Geishofer, G, Binder, A, Müller, M, Zöhrer, B, Resch, B, Müller, W, Faber, J, Finn, A, Endler, G, 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 2005, '4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia', European Journal of Pediatrics, vol. 164, no. 8, pp. 486-490. https://doi.org/10.1007/s00431-005-1673-4

TY - JOUR

T1 - 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia

AU - Geishofer, Gotho

AU - Binder, Alexander

AU - Müller, Martin

AU - Zöhrer, Bettina

AU - Resch, Bernhard

AU - Müller, Wilhelm

AU - Faber, Jörg

AU - Finn, Adam

AU - Endler, Georg

AU - Mannhalter, Christine

AU - Zenz, Werner

AU - Töpke, Bärbel

AU - Fucik, Peter

AU - Penzien, Johann M.

AU - Diab, Gedeon

AU - Miething, Robert

AU - Deeg, K. H.

AU - Hammer, Jürg

AU - Heininger, Ulrich

AU - Varnholt, Verena

AU - Schmidt, Andreas

AU - Bindl, Lutz

AU - Sillaber, Ursula

AU - Huemer, Christian

AU - Meier, Primrose

AU - Simic-Schleicher, G.

AU - Markart, Markus

AU - Pfau, Eberhard

AU - Broede, Hans

AU - Ausserer, Bernd

AU - Kalhoff, Hermann

AU - Arpe, Volker

AU - Schweitzer-Krantz, Susanne

AU - Kasper, Johannes Martin

AU - Loranth, Kathrin

AU - Bittrich, Hans J.

AU - Simmer, Burkhard

AU - Weigand, Nicola

AU - Herting, Egbert

AU - Smolle, Karl Heinz

AU - Fusch, Christoph

AU - Gruber, Alois

AU - Schimmel, Ulf

AU - Knaufer-Schiefer, Suzanne

AU - Lässig, Wolfgang

AU - Hennenberger, Axel

AU - Von Der Wense, Axel

AU - Tillmann, Roland

AU - Schwarick, Jürgen

AU - Sitzmann, F. C.

AU - Müller, Herbert

AU - Kurnik, Peter

AU - Groneck, Peter

AU - Gröblacher-Roth, Helene

AU - Bensch, Jürgen

AU - Moser, Reinhard

AU - Schwarz, Rudolf

AU - Lenz, Kurt

AU - Hofmann, Thomas

AU - Göpel, Wolfgang

AU - Berger, Thomas

AU - Hauser, Erwin

AU - Förster, Kai Martin

AU - Peters, Jochen

AU - Nicolai, Thomas

AU - Kumlien, Björn

AU - Beckmann, Regina

AU - Seitz, Christiane

AU - Hüseman, D.

AU - Schürmann, Roland

AU - Ta, Van Hop

AU - Weikmann, Eckart

AU - Evert, W.

AU - Hautz, Jürgen

AU - Seidenberg, Jürgen

AU - Wocko, Lucia

AU - Luigs, Petra

AU - Reiter, Hans Ludwig

AU - Quietzach, J.

AU - König, Michael

AU - Herrmann, Johanna

AU - Mitter, Horst

AU - Seidler, Ekkehard

AU - Maak, Bernhard

AU - Sperl, Wolfgang

AU - Meissl, Manfred

AU - Koch, Reinhard

AU - Cremer, Manfred

AU - Breuer, H. A.

AU - Görke, W.

AU - Nossal, Robert

AU - Pernice, Walter

AU - Salzer, Hans R.

AU - Koch, Hartmut

AU - Schaller, Gerhard

AU - Paky, Franz

AU - Straßer, Friedrich

AU - Eitelberger, Franz

AU - Sontheimer, D.

AU - Lischka, Andreas

AU - Dilch, Alfred

AU - Scheibenpflug, Christian

AU - Bruckner, Robert

AU - Runge, Klaus

AU - Kunze, Wolfgang

AU - Schermann, Peter

N1 - Funding Information: Acknowledgements This study was supported by the Jubiläumsfond der Österreichischen Nationalbank, grants 8842 and 10112. Copyright: Copyright 2013 Elsevier B.V., All rights reserved.

PY - 2005/7

Y1 - 2005/7

N2 - 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. Previously, an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1gene in a cohort of UK and Dutch children with meningococcal sepsis was reported. We carried out a prospective, multicentre study to investigate the association of the 4G/5G PAI-1 polymorphism, diagnosis, and outcome in meningococcal disease in a Central European and UK population. Blood samples and clinical information of 347 previously healthy children with meningococcal infection were collected from 95 paediatric hospitals in Germany, Switzerland, Italy, the United Kingdom, and Austria from 2000 until 2002. Mortality was significantly associated with the 4G/4G genotype (12 of 90 (13%) vs. 15 of 240 (6%), P =0.037), resulting in an odds ratio of 2.31. The diagnosis of sepsis (independent of symptoms of meningitis) was significantly more frequent in carriers of the 4G/4G genotype (P =0.01), resulting in an odds ratio of 2.21 to develop sepsis. Meningitis was not associated with the PAI-1 4G/5G polymorphism, and allele frequencies were similar in patient and control groups. Conclusion:Our data show a correlation between the 4G/4G genotype in the plasminogen activator inhibitor-1 gene and poor outcome in children with meningococcal infection. In addition, 4G homozygous patients were prone to develop sepsis. We found no influence of the plasminogen activator inhibitor-1 polymorphism on the susceptibility to invasive meningococcal infection.

AB - 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. Previously, an association between mortality and the functional 4G/5G promoter polymorphism of the PAI-1gene in a cohort of UK and Dutch children with meningococcal sepsis was reported. We carried out a prospective, multicentre study to investigate the association of the 4G/5G PAI-1 polymorphism, diagnosis, and outcome in meningococcal disease in a Central European and UK population. Blood samples and clinical information of 347 previously healthy children with meningococcal infection were collected from 95 paediatric hospitals in Germany, Switzerland, Italy, the United Kingdom, and Austria from 2000 until 2002. Mortality was significantly associated with the 4G/4G genotype (12 of 90 (13%) vs. 15 of 240 (6%), P =0.037), resulting in an odds ratio of 2.31. The diagnosis of sepsis (independent of symptoms of meningitis) was significantly more frequent in carriers of the 4G/4G genotype (P =0.01), resulting in an odds ratio of 2.21 to develop sepsis. Meningitis was not associated with the PAI-1 4G/5G polymorphism, and allele frequencies were similar in patient and control groups. Conclusion:Our data show a correlation between the 4G/4G genotype in the plasminogen activator inhibitor-1 gene and poor outcome in children with meningococcal infection. In addition, 4G homozygous patients were prone to develop sepsis. We found no influence of the plasminogen activator inhibitor-1 polymorphism on the susceptibility to invasive meningococcal infection.

UR - http://www.scopus.com/inward/record.url?scp=23044459987&partnerID=8YFLogxK

U2 - 10.1007/s00431-005-1673-4

DO - 10.1007/s00431-005-1673-4

M3 - Journal articles

C2 - 15843979

AN - SCOPUS:23044459987

SN - 0340-6199

VL - 164

SP - 486

EP - 490

JO - European Journal of Pediatrics

JF - European Journal of Pediatrics

IS - 8

ER -

4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia

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