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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 于明暉(Ming-Whei Yu) | |
dc.contributor.author | Ching-Fang Tsai | en |
dc.contributor.author | 蔡青芳 | zh_TW |
dc.date.accessioned | 2021-06-07T18:08:10Z | - |
dc.date.copyright | 2012-09-17 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-17 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16285 | - |
dc.description.abstract | 研究背景: 在台灣大約有80%肝細胞癌(HCC)病例可歸因於B型肝炎病毒慢性感染。B型肝炎之高病毒量對於進展為肝細胞癌是個證據充分的危險因子。一篇全基因體關聯性研究定義出數個位在人類白血球抗原(HLA)-DP基因區上的單核苷酸多型性(SNPs)與慢性B型肝炎感染相關,並且已有許多研究驗證該發現。因此,本研究目在於利用家族研究來評估4個HLA-DP SNPs與B型肝炎病毒量控制及HCC危險性之關係。並且探討這之間的關係是否受到性別、病毒基因型及生活習慣等因素之潛在修飾作用影響。
材料方法: 我們使用先前已發表的家族研究中,共250個家庭、包含258個手足集合以評估HLA-DP SNPs在HBV病毒量控制所扮演的角色。而在這些家庭中,共有144對病例-未罹病手足配對進入HCC相關性分析。 結果: rs3077與男性早發HCC (定義為<50歲)有顯著相關(AG/AA vs. GG基因型OR=0.40,95% CI=0.17-0.94,P=0.0357),但在女性中無顯著相關。其他SNPs並沒有觀察到類似的相關,而且也沒有發現這4個HLA-DP SNPs與晚發HCC有關。分析HLA-DP SNPs與HBV病毒量的部分,我們發現rs3128917帶有TG或TT基因型的人與HBV≧4.662 log copies/ml之高病毒量有負相關,其校正過後的OR值為0.64 (95% CI=0.46-0.89,p=0.0081)。而分層分析的部分,發現男性、感染HBV基因型C個案、HBeAg陰性個案、抽菸者及飲酒者也有類似的相關性。 結論: HLA-DP基因區上的變異在HCC家庭具有控制病毒量之作用,並且在進展為HCC上扮演著某些角色。 | zh_TW |
dc.description.abstract | Background and Aims: In Taiwan, a proximately 80% of hepatocellular carcinoma (HCC) cases are attributable to chronic hepatitis B virus (HBV) infection. High level of HBV viral load has been well documented as a risk factor for progression to HCC. A genome-wide association study identified several single-nucleotide polymorphisms (SNPs) in HLA-DP region associated with chronic HBV infection, and this finding has been replicated in following studies. The aim of this study was to investigate the relationships between four HLA-DP SNPs and HBV viral load and HCC risk using a family-based study. The potential modification effects on these relationships by sex, viral genotype and lifestyle factors were also explored.
Methods: We used data from a previously published family-based study involving a total of 250 families containing 258 sib sets to determine the role of HLA-DP SNPs in control of HBV viral load. Of these families, 144 case-unaffected sib pairs were included in the analysis of HCC. Results: rs3077 was significantly associated with early-onset HCC (defined as <50 years) in males (AG/AA vs. GG genotype: OR=0.40, 95% CI=0.17-0.94, p=0.0357) but not in females. No such association was observed for other SNPs, and there were no associations between all the four HLA-DP SNPs and late-onset HCC. In analysis of HLA-DP SNPs and HBV viral load, SNP rs3128917 carried TG or TT genotype was inversely associated with a high viral load of ≧4.662 log copies/ml, with an adjusted OR of 0.64 (95% CI=0.46-0.89, p=0.0081). In stratified analysis, this association was only observed in males, HBV genotype C group, HBeAg-negative subjects, cigarette smokers and alcohol drinkers. Conclusions: We suggest that the genetic variation in the HLA-DP region may be involved in the control of HBV viral load and play some role in the development of HCC in HCC families. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T18:08:10Z (GMT). No. of bitstreams: 1 ntu-101-R99849008-1.pdf: 1107595 bytes, checksum: b3a20c9b5117c6ab6f0e350c206062b0 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 目錄
致謝 I 中文摘要 II Abstract III 目錄 i 圖表目錄 ii 研究背景 1 材料方法 7 結果 10 討論 13 參考文獻 19 附錄一 35 附錄二 36 圖表目錄 表 一 家族相關性研究: 人口學特徵、病毒因子及肝臟生化指標 24 表 二 早發與晚發肝細胞癌家庭病例及未罹病手足之人口學特徵、病毒因子及肝臟生化指標 25 表 三 HLA-DP SNPs 之基因型頻率分布 26 表 四 HLA-DP SNPs之連鎖不平衡 27 表 五 條件邏輯迴歸分析: HLA-DP SNPs 與早發及晚發肝細胞癌之關係 28 表 六 HLA-DP SNPs Dominant Model與性別、病毒及環境因子之交互作用對於早發肝細胞癌的效應 29 表 七 廣義估計方程式: HLA-DP SNPs與病毒量之關係 30 表 八 HLA-DP SNPs Dominant Model與性別、病毒及環境因子之交互作用對於病毒量之效應(連續變項) 31 表 九 HLA-DP SNPs Dominant Model與性別、病毒及環境因子之交互作用對於病毒量之效應(以4.386 log copies/ml為切點) 32 表 十 HLA-DP SNPs Dominant Model與性別、病毒及環境因子之交互作用對於病毒量之效應(以4.662 log copies/ml為切點) 33 圖 一 研究對象之流程圖 34 | |
dc.language.iso | zh-TW | |
dc.title | 人類白血球抗原-DP基因變異與B型肝炎病毒量及肝細胞癌之關係:家族研究 | zh_TW |
dc.title | Association of HLA-DP Genetic Variation, Viral Load, and Hepatocellular Carcinoma in Chronic Hepatitis B: Family-Based Study | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 王姿乃(Tsu-Nai Wang),陳保中(Pau-Chung Chen),蔡孟勳(Mong-Hsun Tsai) | |
dc.subject.keyword | 人類白血球抗原(HLA)-DP,單核苷,酸多形性(SNPs),家族研究,B型肝炎病毒量,肝細胞癌, | zh_TW |
dc.subject.keyword | Human Leukocyte Antigen (HLA)-DP,single-nucleotide polymorphism (SNP),family-based study,HBV viral load,hepatocellular carcinoma, | en |
dc.relation.page | 36 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2012-07-18 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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