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, Central European Meningococcal Genetic Study Group

Research output: Contribution to journalArticle (Academic Journal)peer-review

60 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 languageEnglish
Pages (from-to)486-90
Number of pages5
JournalEuropean Journal of Pediatrics
Volume164
Issue number8
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Odds Ratio
  • Gene Frequency
  • Polymorphism, Genetic
  • Humans
  • Austria
  • Child
  • Switzerland
  • Italy
  • Great Britain
  • Child, Preschool
  • Genotype
  • Infant
  • Promoter Regions, Genetic
  • Guanine
  • Prospective Studies
  • Meningococcal Infections
  • Adult
  • Plasminogen Activator Inhibitor 1
  • Adolescent
  • Germany
  • Male
  • Female

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