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Binder, A; Endler, G; Rieger, S; Geishofer, G; Resch, B; Mannhalter, C; Zenz, W; Central European Meningococcal Genetic Study Group.
Protein C promoter polymorphisms associate with sepsis in children with systemic meningococcemia.
Hum Genet. 2007; 122(2):183-190 Doi: 10.1007/s00439-007-0392-5 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Binder Alexander
Zenz Werner
Co-Autor*innen der Med Uni Graz
Resch Bernhard
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Abstract:
Meningococcal disease may present as sepsis, meningitis or a combination of both. Protein C (PC) is an important regulator of thrombin activity. Two polymorphisms in the promoter region of PC (C-1654T, A-1641G) have been shown to affect PC levels. In patients with meningococcal sepsis, low PC levels have been correlated with increased severity and poor outcome. We established a multicenter case-control study to determine whether PC promoter polymorphisms are associated with occurrence and outcome of meningococcal disease and sepsis. 288 previously healthy children with meningococcal infection from 97 pediatric hospitals in Germany, Switzerland, Italy, and Austria and 309 healthy controls were included in the study. A strong age-dependant effect was found. Patients younger than 1 year carried significantly more often the CG-CG genotype than healthy controls (28.6% vs. 17.8%, P = 0.04). Carriers of the CG allele showed a 3.43-fold increased odds ratio (OR) to develop sepsis (95% CI: 1.05-11.20; 85.7% vs. 63.6%, P = 0.036). The TA-TA genotype conferred a protective role for the development of sepsis (P = 0.017) with a Haldane OR of 0.09 (95% CI: 0.01-0.94). Systolic blood pressure values were significantly decreased in patients carrying the CG-CG genotype (70 vs. 86 mmHg, P = 0.005), and the need for adrenergic support significantly higher (70% vs. 26%, P = 0.018), resulting in an OR of 6.61 (95% CI: 1.28-34.14). These findings show that in young children PC promoter genotype is associated with susceptibility for meningococcal disease, the development of meningococcal sepsis, lower blood pressure, and need for adrenergic support.
Find related publications in this database (using NLM MeSH Indexing)
Adolescent -
Age Factors -
Blood Pressure -
Child -
Child, Preschool -
DNA Primers - genetics
DNA Primers -
Gene Frequency -
Genotype -
Humans -
Infant -
Infant, Newborn -
Meningococcal Infections - complications
Odds Ratio -
Polymorphism, Single Nucleotide - genetics
Promoter Regions, Genetic - genetics
Protein C - genetics
Sepsis - etiology
Sepsis - genetics

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