Protein C promoter polymorphisms associate with sepsis in children with systemic meningococcemia.
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.
Binder
Alexander
A
Department of General Pediatrics, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria.
Endler
Georg
G
Rieger
Sandra
S
Geishofer
Gotho
G
Resch
Bernhard
B
Mannhalter
Christine
C
Zenz
Werner
W
D000293:Adolescent; D000367:Age Factors; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D005060:Europe; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008589:Meningococcal Infections / Q000150:complications*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011486:Protein C / Q000235:genetics*; D018805:Sepsis / Q000209:etiology* / Q000235:genetics*
D017931:DNA Primers; D011486:Protein C