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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; Central European Meningococcal Genetic Study Group.
4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia.
Eur J Pediatr. 2005; 164(8):486-490 Doi: 10.1007/s00431-005-1673-4
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Leading authors Med Uni Graz
Zenz Werner
Co-authors Med Uni Graz
Binder Alexander
Müller Martin
Müller Wilhelm
Resch Bernhard
Zöhrer Bettina
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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. 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.
Find related publications in this database (using NLM MeSH Indexing)
Adolescent -
Adult -
Austria - epidemiology
Child -
Child, Preschool -
Female -
Gene Frequency -
Genotype -
Germany - epidemiology
Guanine -
Humans -
Infant -
Italy - epidemiology
Male -
Meningococcal Infections - blood
Meningococcal Infections - diagnosis
Meningococcal Infections - genetics
Meningococcal Infections - mortality
Odds Ratio -
Plasminogen Activator Inhibitor 1 - genetics
Polymorphism, Genetic -
Promoter Regions, Genetic - genetics
Prospective Studies -
Switzerland - epidemiology
United Kingdom - epidemiology

Find related publications in this database (Keywords)
fibrinolysis
meningococcal disease
plasminogen activator inhibitor-1
polymorphism
sepsis
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