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系統識別號 U0026-0302201713373200
論文名稱(中文) 慢性B型肝炎病人肝指數異常與單核苷酸多態性之相關性研究
論文名稱(英文) Identification of single nucleotide polymorphism associated with elevated alanine aminotransferase for chronic hepatitis B patients
校院名稱 成功大學
系所名稱(中) 臨床醫學研究所碩士在職專班
系所名稱(英) Institute of Clinical Medicine(on the job class)
學年度 105
學期 1
出版年 106
研究生(中文) 邱宏智
研究生(英文) Hung-Chih Chiu
學號 S97031014
學位類別 碩士
語文別 中文
論文頁數 39頁
口試委員 指導教授-張定宗
召集委員-楊孔嘉
口試委員-林聖翔
中文關鍵字 B型肝炎  單核苷酸多態性(SNP)  肝指數(ALT)  IL-19  IL-20 
英文關鍵字 Hepatitis B virus (HBV)  alanine aminotransferase (ALT)  single nucleotide polymorphism (SNP)  interleukin-19 (IL-19)  interleukin-20 (IL-20) 
學科別分類
中文摘要 B型肝炎是全世界一個重大的公共衛生問題,百分之七十五的病人集中在亞太地區,台灣也是屬於高盛行區,而B型肝炎所造成的肝硬化以及肝癌仍高居國人死因的前茅。在B型肝炎的自然病程中,病毒與宿主免疫系統的交互作用下,造成肝臟細胞持續或反覆的發炎壞死,是影響B型肝炎患者預後的重要因子,因此臨床治療上,肝指數的上升是一個影響治療的重要指標。目前有許多基因的研究顯示,宿主的基因單核苷酸多態性(SNP)與B型肝炎有密切的相關,包含是否容易感染B型肝炎或自發性清除、對B肝炎疫苗的反應、以及B型肝炎患者長期預後如肝硬化與肝癌的風險,但目前尚未有與肝指數上升之相關性研究,因此,B型肝炎患者單核苷酸多態性與肝指數的關聯性值得進一步探討。
我們一共挑選了124個與B型肝炎有關的基因單核苷酸多態性,並納入447位B型肝患者,分析肝指數上升的風險因子與基因單核苷酸多態性的關聯。本研究發現,在多變數校正後,B型肝炎患者的IL-19與IL-20的單核苷酸多態性rs2243191以及rs1713239,與肝指數上升相關。在合併B型肝炎病毒濃度高低後,我們發現在B型肝炎病毒濃度超過10的6次方copies/mL的患者身上,同時帶有rs2243191 TC/TT型與rs1713239 GG型的人,在肝指數上升高於正常值上限兩倍方面,有最高的風險,為風險最低的rs2243191 CC合併rs1713239 CC/CG患者的4.17倍 (p = 0.004)。我們同時也發現IL-19/20 haplotype、IL-20 haplotype與rs2243191-rs1713239組成的haplotype皆與肝指數上升相關。
總結來說,在B型肝炎患者身上IL-19與IL-20的單核苷酸多態性以及haplotype,可能會影響肝臟發炎的狀況,未來有待進一步驗證此結論以及探討發生的機轉。
關鍵字:B型肝炎、單核苷酸多態性(SNP)、肝指數ALT、IL-19、IL-20
英文摘要 In Taiwan, hepatitis B virus (HBV) related complications are still the leading causes of death. Complex interaction between virus and host immune system determine the severity of inflammation in the natural course of HBV. Elevated alanine aminotransferase (ALT), the serum marker for liver necroinflammation, is a risk factor and predictor of outcomes. Multiple studies have demonstrated that the single nucleotide polymorphisms (SNPs) are associated with HBV outcomes. However, the effect of SNPs on the ALT change is still unknown. The study is to analyze the association of SNPs and ALT elevation in HBV patients. We retrospectively enrolled HBV patients from three hospitals and DNA was extracted from previous residual blood samples. The SNP candidates were chosen according to NCBI-dbGaP and literature review. After adjusted by sex, age, HBV DNA and HBeAg status, IL-19 SNP rs2243191 and IL-20 SNP rs1713239 were found as independent factors of ALT elevation more than two times upper limit of normal (ULN). In patients with DNA > 10E6 copies/mL, those who had both rs2243191 TC/TT type and rs1713239 GG type had 4.17 times risk compared with those who had both rs2243191 CC type and rs1713239 CC/CG type (p = 0.004). Besides, the association with ALT elevation could also be found at IL-19/20, IL-20, and rs2243191-rs1713239 haplotype. We needed further studies to validate the result and to understand the mechanism.
Key words: Hepatitis B virus (HBV), alanine aminotransferase (ALT), single nucleotide polymorphism (SNP), interleukin-19 (IL-19), interleukin-20 (IL-20)
論文目次 目錄
中文摘要………………………………….…………………………..…….....I
Extended Abstract………………………………….…………………..……III
誌謝……………………………………………………………………….…VI
目錄 ……………………………………………….……………………....VII
表目錄 ……………………………………………….………………...…VIII
圖目錄 ……………………………………………….……………………..IX
符號與縮寫對照表…………………………………………………………..X
第一章 緒論 ……………………………….…………………...………1
第二章 材料與方法
一、 研究對象納入 …………………………….………………….......7
二、 SNP的挑選與檢驗方法 ………………………….……………...8
三、 統計分析方法 ………………………….……………………….10
第三章 研究結果與討論
一、 研究結果 ………………………….………………….................11
二、 討論 ………………………….………………….........................15
三、 結論 ……………………………………………………………..19
參考文獻 ………………………….…………………..................................20
附錄 ………………………….…………………...……………….……......25
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