Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/25246
標題: 利用多重式微序列法分析敗血症患者基因型
Genotyping of TNF-α, IL-6, IL-10 and IL-18 Genes in Septicemia Patients by Multiplex-Minisequencing
作者: 李威寰
Lee, Wei-Huan
關鍵字: Sepsis;敗血症;Multiplex minisequencing;Single nucleotide polymorphisms;多重式微序列分析法;單一核甘酸多態性
出版社: 動物科學系所
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摘要: 
本試驗之目的在探討人類基因單一核甘酸多態性與敗血症患者發炎反應性狀之相關性,分析包含於人類腫瘤壞死因子α (tumor necrosis factor-α,TNF-α)、介白素-6 (interleukin-6,IL-6)、介白素-10 (interleukin-10,IL-10)及介白素-18 (interleukin-18,IL-18)等四個候選基因的七個基因型。先以軟體設計專一性引子對,經過PCR反應增殖標的DNA後,分別以PCR-SSCP、PCR-RFLP、微序列法與多重式微序列法進行基因型鑑定。建立以多重式微序列法開發出能於單一試管內同時鑑定多個SNPs標記之DNA檢測平台,檢測之結果與其他方法相符,顯示多重式微序列分析法之可靠性。以此方法檢測之結果分析台灣署立南投醫院重症加護病房敗血症患者各基因之基因型與交替基因頻率分佈,結果發現在TNF-α基因G-308A的GG基因型患者其存活天數以及存活率皆優於GA型,故知G交替基因有利存活;IL-6基因G-174C的GG基因型患者其存活天數以及存活率皆優於GC型,故知G交替基因有利存活;IL-10基因G-1082A的AA基因型患者其存活率優於GA型,故知A交替基因有利存活;IL-18基因之基因型同時為C-607A與G-137C雜合型之患者擁有最高的存活率,且各基因中較有利於存活的基因型亦符合已發表文獻之研究結果。進一步探討台灣署立南投醫院重症加護病房敗血症患者各性狀與臨床觀察指標、基因型存活率之相關性,結果發現TNF-α基因G-308A的GG型患者較之GA型患者、IL-6基因G-174C的GG型患者較之GC型患者、IL-10基因G-1082A的AA型患者較之GA型患者,存活率皆顯著較高(p < 0.05)。TNF-α基因G-308A的GA型患者其第一天血中IL-10濃度遠較GG型患者高(p < 0.05);肌酸酐 (creatinine)也高出GG型患者2倍以上(p < 0.05),顯示腎功能極差,呼應先前文獻指出GA型患者死亡率較高之結果。本試驗建立之多重式微序列分析法以一毛細管同時檢測多個基因的方法,較之傳統的單一核甘酸檢測方法,具有快速、正確及降低成本等優勢,應可應用於人體或動物生理病理特性之相關分析。

The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) with traits relative to inflammatory process in septicemia patients. Genotyping of TNF-α, IL-6, IL-10 and IL-18 genes were carried out by PCR-SSCP, PCR-RFLP, minisequencing and multiplex minisequencing. Specific primer pairs were designed by GCG sequence analysis software and each of the target genes was amplified. The results showed that the multiplex-minisequencing method was able to unambiguously and simultaneously genotyping many SNP loci in one microtubes. Genotypic and allelic frequencies of each gene were analyzed. The results revealed that the survival day and survival rate of GG type of TNF-α (G-308A), GG type of IL-6 (G-174C) were better than the other types in septic patients in the Nantou Hospital. The survival rate of AA type of IL-10 (G-1082A) was higher than GA type. Patients with both of CA type of IL-18 (C-607A) and GC type of IL-18 (G-137C) have the highest survival rate. According to above evidence revealed G allele of TNF-α (G-308A), G allele of IL-6 (G-174C) and A allele of IL-10 (G-1082A) were most advantageous for survival. Patients with GG type of TNF-α (G-308A), GG type of IL-6 (G-174C), and AA type of IL-10 (G-1082A) have a higher survival rate than other types (p <0.05). Patients with GA type of TNF-α (G-308A) have a higher serum IL-10 level at entry (p < 0.05). These patients also have doubled serum creatinine represents poor renal functions than GG type patients. It may be one reason for higher mortality happened to GA type patients revealed from previous studies. We have successfully developed a rapid, accuracy and cost-effective for genotyping many loci in the same capillary tube. These results could be useful for human body or animal physiological and pathological analysis.
URI: http://hdl.handle.net/11455/25246
其他識別: U0005-2607200910593600
Appears in Collections:動物科學系

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