Project title
敗血症之基因多型性研究(I)
Internal ID
NSC94-2314-B002-282
Principal Investigator
Start Date
August 1, 2005
End Date
July 12, 2006
Investigators
Organizations
Partner Organizations
Project Web Site
Genetic Polymorphism of Sepsis (I) = 敗血症之基因多型性研究 (I)
Keywords
sepsis
genetic polymorphism
Description
Sepsis and its sequelae are still a major cause of morbidity and mortality on today』s intensive care units. Many endogenous mediators were found to mediate the individual』s response to infection and the course of the diseases. Sepsis can be viewed as a complex polygenetic disorder, with many genes collaborating at different loci. The role of an individual』s genetic background and predisposition for the extent of inflammatory responses is determined by variabilities of genes encoding endogenous mediators or signal molecules that constitute the pathway of inflammation. Hence genomic information may be used to identify groups of patients with a high risk of developing severe sepsis and multiple organ dysfunctions. Many genetic polymorphisms were reported to be associated with different outcomes in sepsis. However, the associations were not consistently reproducible. The possible explanations related to irreproducibility of most association studies could be many, one explanation is that weak genetic effects combined with underpowered studies may render falsely negative reports. Increasing the sample size to up to at least 500 individuals is considered to improve the power of association studies. The study, by using large sample size admitted into the medical intensive care unit of our hospital and approach with single nucleotide polymorphism assay, is carried out to investigate the association between candidate genes and the baseline characteristics, or outcome of sepsis. We intend to complete evaluating 30 SNPs of 9 candidate genes related to the key pathogenesis (inflammation and coagulation) of sepsis: BPI (Bactericidal/permeability increasing protein), LBP (Lipopolysaccharide binding protein), CD14 receptor, TLR4 (Toll-like receptor 4), TLR2 (Toll-like receptor 2), THBD (Thrombomodulin), EPCR (Endothelial protein C receptor), PAR1 (Protease activated receptor 1), PAI-1 (Plasminogen activator inhibitor-1) in at least 1,000 subjects with sepsis within two year. The findings are expected to stratify the risk of sepsis patients to specific outcome, or response to specific therapy.