Association of IL-1β and IL-1RN Gene Polymorphisms between HBV Infection and the Development of Hepatocellular Carcinoma

B型肝炎是一種發生在人類的主要疾病，在全世界約有二十億人曾經感染過B型肝炎病毒，B型肝炎是由B型肝炎病毒感染而引起的肝臟發炎；三分之一的肝硬化和二分之一的肝癌其致病原因，可以歸因為B型肝炎病毒的感染，每年由於B型肝炎病毒而導致死亡的約有五十至七十萬人。 B型肝炎病毒感染被認為與原發性肝癌有關，B型肝炎帶原者會得到肝癌的機率，比非帶原者高一百倍；在此引發出一種假設，在這群B型肝炎帶原者中，有一個分類的界線，界線的一邊是帶原而後發生肝癌，另一邊則是帶原但不因此發生肝癌；這樣的概念與現在的SNP (Single Nucleotide Polymorphism) 的應用不謀而合，利用單一或數個SNP的型別不同，可以將一個族群劃分為數個小群，藉此分析其疾病易感性的不同或是族群演化過程。在高加索人和台灣人的族群中，IL-1β和IL-1RN之型別所佔比例明顯不同。此外，IL-1的多型性被認為與增加胃癌發生機率有關。 利用兩組不同的群組來進行比較；第一組對照組，是曾受過B型肝炎病毒感染，血液檢驗結果呈現HBsAg陽性，沒有發生肝癌的帶原者，此組共有183人；第二組發病組，是曾受過B型肝炎病毒感染，血液檢驗結果呈現HBsAg陽性，罹患肝癌的病人，此組共有183人；此兩組的檢體取樣，另同時兼顧兩群組中年齡及性別比例趨於接近。 進行IL-1β –511、IL-1RN 3575、IL-1RN 9261和IL-1RN 11100此四個SNP型別鑑定，並對此四個SNP進行allele、genotype及SNP之間作用等分析比較。其中IL-1β –511與IL-1RN 9261，和IL-1RN 9261與IL-1RN 11100，此兩組SNP之間處於連鎖不平衡，因此針對此兩組SNP進行haplotype分析。 經由比較對照組與發病組的四個SNP的allele、genotype、以及兩組SNP之間haplotype此三項的頻率後，兩組間並無顯著差異。Hepatitis B is one of the major diseases of mankind. Worldwide, two billion people have been infected with hepatitis B virus (HBV), 360 million have chronic infection, and 500,000-700,000 die each year from HBV-related liver disease or hepatocellular carcinoma. Approximately one third of all cases of cirrhosis and half of all cases of hepatocellular carcinoma can be attributed to chronic HBV infection. HBV infection is its link to primary hepatocellular carcinoma. Chronically infected subjects have a risk of hepatocellular carcinoma that is 100 times as high as that for non-carriers. However, some of HBV carrier will become to case of hepatocellular carcinoma. It could be considered that all HBV carriers can be separated by a line. One part of carriers will be case of hepatocellular carcinoma, and another part of carriers will never be. Try to find out the line, the concept, is closed to using of SNP(Single Nucleotide Polymorphism). The frequency of IL-1Ra allele and IL-1β allele were significantly different in Taiwanese and Caucasians. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. IL-1β –511、IL-1RN 3575、IL-1RN 9261 and IL-1RN 11100, 4 SNPs were analyzed among 183 HBV carriers (the control group) and 183 patients with hepatocellular carcinoma (the case group). IL-1β –511/IL-1RN 9261 and IL-1RN 9261/IL-1RN 11100, they are in linkage disequilibrium. Therefore, they are analyzed in haplotype. In allele frequencies, genotype frequencies and haplotype frequencies, these analyses of 4 SNPs are not different in control group and case group.口試委員簽名頁 2 致謝 3 目錄 4 一、 中文摘要 5 二、 英文摘要 6 三、 緒論 7 四、 研究方法與材料 9 五、 結果 12 六、 討論 14 七、 參考文獻 16 八、 圖表 1