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Title: | 免疫抗原決定位之胺基酸多型性與慢性 B 肝急性發作之關係:縱式研究 Amino Acid Polymorphisms in Immune Epitope and Acute Exacerbation in Chronic Hepatitis B: Longitudinal Study |
Authors: | Szu-Yu Lu 盧思宇 |
Advisor: | 于明暉(Ming-Whei Yu) |
Keyword: | B 型肝炎病毒,急性發作,免疫抗原決定位,胺基酸多型性, hepatitis B virus,acute exacerbation,immune epitope,amino acid polymorphisms, |
Publication Year : | 2012 |
Degree: | 碩士 |
Abstract: | 背景:血清丙氨酸轉胺酶在 B 型肝炎病毒慢性感染期間可能會產生波動,免疫抗原決定位上之胺基酸多型性可能與宿主免疫反應改變相關,本研究針對多個時間點之病毒抗原決定位序列變異與急性發作 (acute exacerbation,AE)之相關性,於慢性 HBV 帶原者中進行病毒全基因體序列分析研究。
材料與方法:研究對象自長期病毒量研究世代中選取 1143 位 HBsAg 陽性且大於 30 歲男性個案,研究對象於收案基線無癌症發生,自 1989 至 1992 年間約每半年至一年追蹤檢查其腹部超音波、肝功能、收取血液檢體並進行其他生化檢查,直到 2006 年為止之收案資料將與全國癌症登記及死亡登記檔連結。 由收案之初即具有序列資料,共 52 急性發作個案(追蹤期間 ALT 峰值≧120 IU/L)中隨機選取追蹤期間 ALT 皆正常之對照組。對照組配對收案年齡(三年內)、HBV 基因型與採檢時間。以 Sanger 定序方法進行全基因體序列分析基線、基線後第一時間點、峰值與峰值後第一時間點等四個時間點。 HBV 基因型則以 MEGA 5.05 軟體建構演化樹作為分類依據 , 勝算比與 95 %信賴區間以廣義線性模式進行運算而得。 結果:本研究發現在不同基因型間具有不同的抗原決定位胺基酸多型性。並搜尋免疫抗原決定位資料庫,找出四個胺基酸變異與急性發作相關之抗原決定位,包含 P 基因區之 RHYLHTLWKAGILYK (OR=0.227, 95%CI=0.05-0.94)、LHLYSHPIILGFRKI (OR=4.8413, 95%CI=1.02-22.9)與 FLLSLGIHL (OR=0.2634, 95%CI=0.08-0.84) ,以及 S 基因區之 FWGPSLYNILSPFMPL (OR=0.2963, 95%CI=0.11-0.79)。此四個抗原決定位胺基酸是否變異與病毒量、抽菸以及 e 抗原具有邊緣性顯著相關,且觀察到在 AE 個案中抗原決定位變異並未隨時間產生改變。 結論: HBV 之聚合酶基因區與表面基因區內的抗原決定位中特定胺基酸多型性可能與急性發作的進程相關。 Background: Serum alanine aminotransferase (ALT) may fluctuate during chronic infection of hepatitis B virus (HBV). Amino acid polymorphism in immune epitope can alter host immune response. We aimed to assess the temporal association between viral epitope sequence variants and the occurrence of acute exacerbation (AE) among chronic HBV carriers through full-length sequence analysis. Methods: Study subjects were obtained from an existing longitudinal viral-load cohort study involving a total of 1143 male HBsAg carriers aged ≥30 years old, who were originally free of cancer at recruitment between 1989 and 1992 and followed by annual clinical evaluation through abdominal ultrasonography and liver biochemistry test and data linkage to the computerized database of national cancer and death registry until Dec. 31, 2006.A total of 52 AE case (ALT peak ≧120 IU/L) with available sequence data at baseline were identified. For each case subject, one control was drawn at random from subjects with normal ALT level. Control subjects were selected to match cases on age (within 3 years) at recruitment, HBV genotype, and blood collection time during follow-up. Full-length HBV genome sequences were analyzed by Sanger sequencing method at three time point, baseline, ALT peak and after ALT peak. HBV genotypes were determined through phylogenetic trees constructed by using Mega 5.05 software. Odds ratios (ORs) and confidence intervals (CIs) were generated by generalized estimating equations. Result: We found different patterns of epitope amino acid polymorphisms between genotypes. By searching immune epitope database, we identified four epitopes amino acid variants were associated with the occurrence of AE, including RHYLHTLWKAGILYK (OR=0.227, 95%CI=0.05-0.94), LHLYSHPIILGFRKI (OR=4.8413, 95%CI=1.02-22.9), and FLLSLGIHL (OR=0.2634, 95%CI=0.08-0.84) in polymerase gene region and FWGPSLYNILSPFMPL (OR=0.2963, 95%CI=0.11-0.79) in surface gene region. The emergences of these four epitope amino acid variants were marginally significant with any other variables, including viral load, smoking and HBeAg. Moreover, those epitope variants did not change over time among AE case. Conclusion: Certain amino acid polymorphism embedded in epitopes in the polymerase and surface genes of HBV may play some role in the indication of acute exacerbation. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16266 |
Fulltext Rights: | 未授權 |
Appears in Collections: | 流行病學與預防醫學研究所 |
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