Impact of Inherited Genetic Variants on Critically Ill Septic Children

Abstract

Sepsis remains an important source of morbidity and mortality in children, despite the development of standardized care. In the last decades, there has been an increased interest in genetic and genomic approaches to early recognition and development of treatments to manipulate the host inflammatory response. This review will present a summary of the normal host response to infection and progression to sepsis, followed by highlighting studies with a focus on gene association studies, epigenetics, and genome-wide expression profiling. The susceptibility (or outcome) of sepsis in children has been associated with several polymorphisms of genes broadly involved in inflammation, immunity, and coagulation. More recently, gene expression profiling has been focused on identifying novel biomarkers, pathways and therapeutic targets, and gene expression-based subclassification. Knowledge of a patient’s individual genotype may, in the not-too-remote future, be used to guide tailored treatment for sepsis. However, at present, the impact of genomics remains far from the bedside of critically ill children.

Keywords

• children
• epigenetics
• gene association studies
• genome-wide expression profiling
• host-pathogen response
• immunity