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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Paediatrics, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria.
authors.forename: Gotho
authors.initials: G
authors.lastname: Geishofer
authors.forename: Alexander
authors.initials: A
authors.lastname: Binder
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.forename: Bettina
authors.initials: B
authors.lastname: Zöhrer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Resch
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Müller
authors.forename: Jörg
authors.initials: J
authors.lastname: Faber
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.forename: Georg
authors.initials: G
authors.lastname: Endler
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
authors.forename: Werner
authors.initials: W
authors.lastname: Zenz
mesh_terms: D000293:Adolescent; D000328:Adult; D001317:Austria / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006147:Guanine; D006801:Humans; D007223:Infant; D007558:Italy / Q000453:epidemiology; D008297:Male; D008589:Meningococcal Infections / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D013557:Switzerland / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D006147:Guanine