Multiple gene-to-gene interactions in children with sepsis: a combination of five gene variants predicts outcome of life-threatening sepsis

INTRODUCTION The aim of the study was to identify the dependency structure of genetic variants that can influence the outcome for paediatric patients with sepsis. METHODS We evaluated the role of single nucleotide polymorphisms for five genes: bactericidal permeability increasing protein (BPI; rs5743507), lipopolysaccharide-binding protein (LBP; rs2232618), toll-like receptor 4 (TLR4; rs4986790), heat shock protein 70 (HSP 70; rs2227956), and interleukin 6 (IL-6; rs1800795) in 598 children aged 0 to 19 years that were admitted to a paediatric intensive care unit with fever, systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, or multiple organ dysfunction syndrome. A control group of 529 healthy individuals was included. Multi-way contingency tables were constructed and statistically evaluated using log-linear models. Typical gene combinations were found for both study groups. RESULTS Detailed analyses of the five studied gene profiles revealed significant differences in sepsis survival. Stratification into high-risk, intermediate-risk, and low-risk groups of paediatric patients can predict the severity of sepsis. CONCLUSIONS Analysis of single nucleotide polymorphisms for five genes can be used as a predictor of sepsis outcome in children.