2005-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647546敗血症的治療至今仍然是重症醫療照護方面非常困難的問題。敗血症可以視為複雜 的基因疾病，臨床表現可由不同基因協調產生。許多內生性的化學物質都被發現和 個體對感染的反應與疾病的進程有關，而決定這些物質合成的基因變異性就可能會 影響到個體對發炎反應的程度，因此基因體的資訊便有助於找出發生嚴重敗血症的 高危險族群。目前一些基因多型性已被發現跟敗血症的預後有關，不過這些基因與 敗血症之相關聯性卻多半無法重現。對此有相當多可能的解釋，其中一個可能是單 一基因的影響效應不大，必須依來較大的樣本數才能看出基因效應。一般認為，若 樣本數能超過五百例，則研究將具有足夠的效力。本研究計畫在利用本院的內科加 護病房數量龐大的病患數得大樣本數的病人檢體以及SNP 分析方式探討目標基因 與敗血症病患特徵與育後之相關性。吾人預計在二年內完成9 個與敗血症發炎與血 液凝固過程有關之基因: 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) 30 個SNP 在至少1000 個樣本數的分析。我們預期這些分析將有助於敗 血病患之臨床分類，包括對特殊藥物的反應。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.敗血症;基因多型性sepsisgenetic polymorphism