Bactericidal permeability increasing protein gene variants in children with sepsis
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To evaluate the role of genetic polymorphisms of the bactericidal permeability increasing protein (BPI) in pediatric patients with sepsis.
Prospective, single-center, case-control study at the pediatric intensive care unit (PICU) of a university hospital.
345 consecutive pediatric patients admitted to the PICU with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ distress syndrome (MODS).
DNA was isolated and two BPI gene polymorphisms BPI (G545 > C) Taq and BPI (A645 > G) 216 were studied in patients and compared with healthy controls.
Measurements and results
Genetic analysis of the BPI Taq gene revealed significant differences between healthy controls and the subgroup of febrile patients (p = 0.0243), the subgroup of SIRS and sepsis (p = 0.0101), and the subgroup of severe sepsis, septic shock, and MODS (p = 0.0027), respectively. No statistically significant differences for the BPI 216 gene polymorphism were found between patient and healthy control groups. A statistically significant predisposition to Gram-negative sepsis in patients carrying the BPI Taq GG variant together with the BPI 216 AG or GG variant was revealed (p = 0.0081), and these haplotypes were also associated with death due to sepsis-related complications.
BPI Taq gene polymorphism is the accurate predictor of the severity of sepsis in children admitted to the PICU.
KeywordsSepsis Bactericidal permeability increasing protein Children Genetic polymorphism Immunity
This work was supported by research project of the Grant Agency of the Czech Republic GACR No. 301/03/D196. We acknowledge J. Michalek Sr. for statistical analysis of data and N. Kugan who reviewed the medical English of this manuscript.
- 1.Parker MM, Fink MP (1992) Septic shock. J Intensive Care Med 7:90–1003Google Scholar
- 2.Andrews P, Azoulay E, Antonelli M, Brochard L, Brun-Buisson C, Dobb G, Fagon JY, Gerlach H, Groeneveld J, Mancebo J, Metnitz P, Nava S, Pugin J, Pinsky M, Radermacher P, Richard C, Tasker R, Vallet B (2005) Year in review in intensive care medicine, 2004. III. Outcome, ICU organisation, scoring, quality of life, ethics, psychological problems and communication in the ICU, immunity and hemodynamics during sepsis, pediatric and neonatal critical care, experimental studies. Intensive Care Med 31:356–372PubMedCrossRefGoogle Scholar
- 5.Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM (2004) Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med 30:536–555PubMedCrossRefGoogle Scholar
- 14.Shu-Zun Q, Yan L, O'Connor CD (1994) The region around residue 115 of human bactericidal/permeability-increasing protein is not involved in lipopolysaccharide binding or bactericidal activity. Biochem J 298:711–718Google Scholar
- 20.Hubacek JA, Stüber F, Fröhlich D, Book M, Wetegrove S, Ritter M, Rothe G, Schmitz G (2001) Gene variants of the bactericidal/permeability increasing protein and lipopolysaccharide binding protein in sepsis patients: gender-specific genetic predisposition to sepsis. Crit Care Med 29:557–561PubMedCrossRefGoogle Scholar
- 24.Multinational monitoring of trends and determinants in cardiovascular diseases: “MONICA Project”. Manual of operations WHO/MNC 82.2, November 1983Google Scholar
- 27.Agresti A (1990) Categorical data analysis. Wiley, New York, pp 42–78Google Scholar
- 29.Leteurtre S, Martinot A, Duhamel A, Proulx F, Grandbastien B, Cotting J, Gottesman R, Joffe A, Pfenninger J, Hubert P, Lacroix J, Leclerc F (2003) Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet 362:192–197PubMedCrossRefGoogle Scholar
- 31.Bindl L, Buderus S, Dahlem P, Demirakca S, Goldner M, Huth R, Kohl M, Krause M, Kuhl P, Lasch P, Lewandowski K, Merz U, Moeller J, Mohamed Y, Peters M, Porz W, Vierzig A, Richard J, Scharf J, Varnholt V, ESPNIC ARDS Database Group (2003) Gender-based differences in children with sepsis and ARDS: the ESPNIC ARDS Database Group. Intensive Care Med 29:1770–1773PubMedCrossRefGoogle Scholar