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研究生:陳思達
研究生(外文):Szu-Ta Chen
論文名稱:兒童幽門桿菌感染的免疫基因多型性研究
論文名稱(外文):The genetic polymorphisms of immunity in children with Helicobacter pylori infection
指導教授:倪衍玄倪衍玄引用關係
指導教授(外文):Yen-Hsuan Ni
口試委員:吳明賢劉俊人
口試委員(外文):MING-SHIANG WU
口試日期:2013-07-31
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:43
中文關鍵詞:幽門桿菌基因多型性
外文關鍵詞:H. pylorisingle nucleotide polymorphism
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研究背景: 幽門桿菌感染是胃潰瘍、十二指腸潰瘍、胃癌和胃淋巴癌的重要影響因子,也是重要的致癌物。幽門桿菌感染主要發生在兒童時期,從雙胞胎研究文獻中發現幽門桿菌感染會受到基因影響(genetic effects),遺傳率(Heritability)估計為0.57-0.67。研究發現幽門桿菌感染和宿主胃部的免疫反應失效有關,免疫相關基因及ABO基因多型性(single nucleotide polymorphism, SNP)是否會影響兒童期幽門桿菌感染的易感性(genetic susceptability),目前仍不清楚。
研究目的:本研究納入10-18歲的兒童,探討比較有幽門桿菌感染和無幽門桿菌感染(對照組)兒童,免疫反應相關基因(IL-1B, IL-8, IL-10)及ABO基因的多型性,以了解兒童期幽門桿菌感染是否存在基因易感性。
研究方法: 本研究在雲林地區經由醫院、社區和學校收案,依照血清免疫試驗(serology test)有無幽門桿菌感染抗體分為2組:(1)實驗組為陽性; (2)對照組為陰性。檢驗血液生化學檢查,以及利用real-time PCR genotyping assay檢測5個基因的SNPs IL-1B-31 (rs1143627)、IL-1B-511 (rs16944)、IL-8-251 (rs4073)、 IL-10-1082 (rs1800896)及ABO (rs505922),比較實驗組與對照組之間的差異。
研究結果: 全部共644位兒童納入本研究,平均年齡為14.0歲,整體幽門桿菌血清陽性率為10.7%。幽門桿菌陽性兒童的年齡較高(P = 0.0195)且血液中鐵(ferrum)較低(P = 0.005),但ferritin沒有顯著差異。多變數分析後,在陽性兒童中,發現IL-1B-31(rs1143627)基因的T allele比率顯著比對照組低(OR = 0.846, 95% CI = 0.012 - 0.067, P = 0.014),而在ABO (rs505922)基因的T allele比率顯著比對照組高(OR = 6.128, 95% CI = 2.381 - 15.769, P < 0.001),而其他幾個基因的SNPs IL-1B-511、IL-8-251及IL-10-1082則在兩組間沒有差異。
結論: 雲林地區青少年兒童幽門桿菌感染血清陽性率為10.7%,陽性兒童血液中鐵濃度較低。帶有ABO (rs505922)基因的T allele的兒童具有幽門桿菌感染的易感性(susceptability),而帶有IL-1B-31(rs1143627) T allele的兒童,則較不具幽門桿菌感染的易感性(susceptability)。


Background: H. pylori is a major pathogen of chronic antral gastritis, peptic ulcer disease, gastric cancer, and gastric B-cell lymphoma. Acquisition of H. pylori infection predominantly occurs during childhood period. Twin studies revealed that the genetic effects might influence the H. pylori infection, with an estimated heritability of 0.57 to 0.67. The success of H. pylori infection is related with the failure of host immune responses. However, the association between host immune gene single nucleotide polymorphisms (SNP) and the susceptability of H. pylori infection is not well understood.

Study aim: We aim to study the genetic polymorphisms of immune response genes (IL-1B, IL-8, and IL-10) and ABO gene between 10 to 18 year-old children with or without H. pylori infection and to understand the genetic susceptability in childhood H. pylori infection .

Materials and methods: Subjects in this study were enrolled from schools, community, or the NTU hospital YunLin branch in YunLin county. Children with major systemic disorders or psychological disorders will be excluded. Based on the serology test result of anti- H. pylori IgG, children were divided into 2 groups: (1) study group with positive infection; (2) control group with negative infection. Biochemistry tests were recorded. The genetic polymorphisms of 5 SNPs of IL-1B-31 (rs1143627), IL-1B-511 (rs16944), IL-8-251 (rs4073), IL-10-1082 (rs1800896), and ABO gene (rs505922) were examined by a real-time PCR genotyping assay. The results were compared between 2 groups.

Results: A total 644 children were enrolled in this study with an average age of 14.0 years. The overall seroprevalence rate of H. pylori was 10.7%. The age was significantly higher and the serum ferrum level was significantly lower in children with positive infection than negative infection (P = 0.0195 and 0.005, respectively). By multivariate analysis, the T allele frequency of IL-1B-31 SNP (rs1143627) was significantly lower in seropositive children than control group (OR = 0.846, 95% CI = 0.012 - 0.067, P = 0.014). The T allele frequency of ABO SNP (rs505922) was significantly higher in seropositive children (OR = 6.128, 95% CI = 2.381 - 15.769, P < 0.001).

Conclusions: The seroprevalence rate of H. pylori infection was estimated 10.7% in adolescence in Yunlin county. Children with T allele of ABO SNP (rs505922) might be susceptible to H. pylori infection, and those with T allele of IL-1B-31 SNP (rs1143627) might be resistant to H. pylori infection.


口試委員會審定書 1
誌謝 2
中文摘要 3
英文摘要 4
目錄 6
表目錄 8
圖目錄 9
第一章 前 言
1.1 幽門桿菌感染的重要性 10
1.2 幽門桿菌感染的盛行率與發生率 10
1.3 幽門桿菌感染的危險因子與傳染途徑 12
1.4 幽門桿菌感染相關的免疫反應 12
1.5 幽門桿菌感染與宿主基因有關 16
第二章 研究方法與材料
2.1 研究設計、收案與分組 17
2.2 檢測幽門桿菌感染 17
2.3 白血球DNA萃取 17
2.4 檢測宿主基因多型性(polymorphisms) 17
2.5 臨床特性和症狀 18
2.6 統計分析 18
第三章 研究結果
3.1 整體受試者特徵及幽門桿菌抗體陽性盛行率 19
3.2 比較實驗組與對照組兒童的特徵及生化檢驗 19
3.3 比較實驗組與對照組兒童的基因多型性 20
3.4實驗組與對照組兒童基因多型性的多變項分析統計 20
第四章 討論
4.1 宿主基因多型性與兒童幽門螺旋桿菌感染風險有關 21
4.2 ABO rs505922基因多型性為何影響幽門螺旋桿菌感染風險 21
4.3 台灣兒童幽門螺旋桿菌感染血清陽性率 22
4.4 幽門螺旋桿菌感染與肥胖的關係 22
4.5 幽門螺旋感染與IL-1基因多型性的關係 22
第五章 結論與展望 24
第六章 參考文獻 25
第七章 表 30
第八章 圖 34
第九章 附錄 39
附錄一、 39



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