Host Genetics and Pediatric Sepsis

Susceptibility to, and outcome from, sepsis in children is highly variable due in part to genetic variation in genes coding for components of the innate immune response. This review article will discuss evidence for the influence of host genetic variability on the susceptibility to, and outcome from, sepsis in children and adults. Polymorphisms in genes coding for proteins involved in the recognition of bacterial pathogens (TLR4, CD-14, Fc RIIa, and mannose binding lectin) and the response to bacterial pathogens (TNF, IL-1 , IL-1 , IL-1RA, IL-6, IL-10, heat shock proteins, ACE, plasminogen activator inhibitor-1) can influence the amount or function of the protein produced in response to bacterial stimuli. Evidence is discussed suggesting that some of these genetic polymorphisms influence the susceptibility to, and outcome from, sepsis. Conclusion: Host genetic variability in the regulatory and coding regions of genes for components of the innate immune system may influence the susceptibility to and/or outcome from sepsis. The disparate results observed in many studies of polymorphisms in sepsis emphasize the need for future studies to be larger, to include the analysis of multiple polymorphisms, and to be better designed with respect to control populations in order to identify the degree of influence that genetic variability has on sepsis.