title: Genetics and genomics in pediatric septic shock.
abstract: OBJECTIVE
  Pediatric septic shock continues to be an important public health problem. Several investigative groups have applied genetic and genomic approaches as a means of identifying novel pathways and therapeutic targets, discovery of sepsis-related biomarkers, and identification of septic shock subclasses. This review will highlight studies in pediatric sepsis with a focus on gene association studies and genome-wide expression profiling.
  
  
  METHODS
  A summary of published literature involving gene association and expression profiling studies specifically involving pediatric sepsis and septic shock.
  
  
  CONCLUSIONS
  Several polymorphisms of genes broadly involved in inflammation, immunity, and coagulation have been linked with susceptibility to sepsis, or outcome of sepsis in children. Many of these studies involve meningococcemia, and the strongest association involves a functional polymorphism of the plasminogen activator inhibitor-1 promoter region and meningococcal sepsis. Expression profiling studies in pediatric septic shock have identified zinc supplementation and inhibition of matrix metalloproteinase-8 activity as potential, novel therapeutic approaches in sepsis. Studies focused on discovery of sepsis-related biomarkers have identified interleukin-8 as a robust outcome biomarker in pediatric septic shock. Additional studies have demonstrated the feasibility and clinical relevance of gene expression-based subclassification of pediatric septic shock.
  
  
  CONCLUSIONS
  Pediatric sepsis and septic shock are increasingly being studied by genetic and genomic approaches and the accumulating data hold the promise of enhancing our future approach to this ongoing clinical problem.
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. hector.wong@cchmc.org
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
mesh_terms: D002648:Child; D057890:Epigenomics; D020869:Gene Expression Profiling; D005819:Genetic Markers / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012772:Shock, Septic / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D005819:Genetic Markers; D017395:Plasminogen Activator Inhibitor 1; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha