Anesthesiology & Pain Medicine >> Research >> Focus Areas >> Outcomes >> The Association Between Innate Immunity Genes...
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Research Focus Areas:
Outcomes

The Association Between Innate Immunity Genes and Outcome Following Sepsis in Children

Principal Investigators

J. H. Kim, M.D., G. P. Jarvik, M.D., D. Jardine, M.D.

Description

Septicemia is the 10th leading cause of mortality among Americans of all ages, and is even higher in the perinatal period. While advances in medicine have dramatically decreased the overall fatality, it remains up to 50% for severe cases. Activation of both the innate and adaptive immune system is necessary for rapid clearance of invading pathogens. Occasionally the body's response is characterized by the systemic inflammatory response syndrome (SIRS), which can lead to disseminated infection, organ failure, shock, and death. It is not well known why some have a deleterious response, and what circumstances are necessary for its propagation. While clinical trials of therapeutics targeting steps in these pathways have been disappointing, promising genetic associations have been found between outcome and single nucleotide polymorphisms (SNPs) associated with innate immunity genes. In most of these studies to date, the designs were small candidate-gene association studies, utilizing only a few SNPs. We propose to use another technique to examine this question. By using 352 tagging single nucleotide polymorphisms (tagSNPs) instead of SNPs, we can account for 1181 total SNPs in 36 genes in this pathway. In addition, most our 90 samples from pediatric sepsis patients are accompanied by parental DNA, which allow for the application of a transmission disequilibrium test (TDT), a test of linkage and association unbiased by population stratification. The most significant loci will then be resequenced, in order to determine all rare and common variants. This will be the most comprehensive test of linkage and association of variants among innate immunity genes, controlled for population stratification. Finally, since the samples have already been collected, this proposal provides an efficient examination of innate immunity markers and pediatric sepsis. The results from this study will allow a better understanding of the involvement of specific innate immunity genes in sepsis outcome, and help identify those at greatest risk of death. Future directions include recruiting more sepsis patients and their parents, and performing serum analysis of gene products to provide further evidence of the functional gene variant.

Outcomes:
Research Projects

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Extubation Failure in Patients with Difficult Airways Study
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The Association Between Innate Immunity Genes and Outcome Following Sepsis in Children
J. H. Kim, M.D., G. P. Jarvik, M.D., D. Jardine, M.D.
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