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研究生:楊惠聿
研究生(外文):Hui-Yu Yang
論文名稱:介白質-4和介白質-13之基因多型性與台灣過敏性病童之關係
論文名稱(外文):Relationship between Taiwanese childhood allergic diseases and genetic polymorphism of interleukin-4 and interleukin-13
指導教授:吳文俊吳文俊引用關係
指導教授(外文):Wen-Jun Wu
學位類別:碩士
校院名稱:中山醫學院
系所名稱:毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:123
中文關鍵詞:介白質-4介白質-13基因多型性過敏性疾病兒童
外文關鍵詞:interleukin-4interleukin-13polymorphismallergic diseasechild
相關次數:
  • 被引用被引用:2
  • 點閱點閱:140
  • 評分評分:
  • 下載下載:11
  • 收藏至我的研究室書目清單書目收藏:1
過敏性疾病,例如氣喘、鼻炎及食物過敏…等等是已開發或開發中國家相當普遍的疾病之一且有逐漸增加的趨勢。主要機轉是經由T細胞一連串作用產生細胞激素、進而調節免疫球蛋白E、肥大細胞、嗜鹼性球、嗜酸性球最後導致發炎反應與疾病的產生。許多因素都會造成過敏性疾病,但就一般而言,環境及遺傳因素是最主要的原因。在本研究中,我們將探討國小學童基因多型性與過敏性疾病(包括氣喘、過敏性鼻炎及氣喘和過敏性鼻炎)之間的關係,其內容所提之過敏疾病組即為氣喘組、過敏性鼻炎組、氣喘和過敏性鼻炎組之族群總和。研究結果顯示,當過敏性疾病患者與對照組比較下,發現其血清總IgE值(total IgE)和血液嗜酸性球數目(eosinophil counts)會增加,但肺功能指標(forced expiratory volumn in the first second,FEV1)在各組中並沒有明顯下降的趨勢。另外,利用酵素結合免疫吸附分析(ELISA-enzyme-linked immunosorbent assay)結果可知,過敏性疾病組、氣喘組、過敏性鼻炎組、氣喘和過敏性鼻炎組與對照組相較之下,IL-4濃度有顯著差異,而血中IL-13濃度所測得結果也是如此。以聚合?連鎖反應(PCR--polymerase chain reaction)和限制片段長度多型性(RFLP--restriction fragment length polymorphism)進行基因多型性分析。經邏輯式回歸分析後,結果顯示,台灣地區國小學童IL-4(C589T、C33T)、IL-4 receptor(R576Q)、IL-13(Q110R、C1055T)基因多型性皆與過敏性疾病、氣喘、過敏性鼻炎、氣喘和過敏性鼻炎的發生沒有相關性;IL-4 receptor(Q551R)基因多型性與氣喘的發生具有相關性(p = 0.0113);IL-4 receptor(I50V)與同時併發氣喘和過敏性鼻炎具有相關性(p = 0.0338);而IL-13 receptor(A1398G)則與過敏性鼻炎的發生具有相關性(p = 0.0131)。另外,將基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、血清介白質-4、介白質-13濃度以邏輯式回歸分析,結果顯示在四組疾病組中,其血清總IgE值、血液嗜酸性球數目、血清介白質-4濃度均有顯著的上升,而介白質-13之濃度則在氣喘組有顯著的差異,但基因多型性在本次研究結果中對於肺功能指標卻沒有顯著的影響。

Allergic diseases, such as asthma, rhinitis and food allergics, are reaching epidemic proportions in both developed and developing world. The mechanism of allergy is a polarization of T-lymphocyte responses, and enchanced secretion of cytokines involved in regulation of immunoglobulin E, mast cells, basophils and eosinophiles, leading to inflammation and diseases. Although many factors are important to the development of atopy, the environmental and hereditary factors are the strong ones, especially some genes and chromosomal regions were reported been linked to allergy. To determine the polymorphism of interleukin-4(IL-4) and interleukin-13(IL-13) for the development of atopy, asthma, and allergic rhinitis, 514 subjects were identified, to whom 120 were controls, 394 were allergy patients divided to three groups - 90 subjects were asthma cases, 119 subjects were allergic rhinitis and 185 were both asthma and allergic rhinitis. Compared with controls, the serum total IgE and eosinophil counts were increased in allergic patients, but the forced expiratory volumn in the first second(FEV1), did not decreased. The enzyme-linked immunosorbent assay(ELISA) showed the IL-4 and IL-13 concentration were increased in allergic patients, asthma patients, allergic rhinitis patients and both asthma and allergic rhinitis patients. All the subjects were analyzed polymorphism by polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP). The statistical data showed the polymorphism of IL-4 ligand(C589T、C33T), IL-4 receptor(R576Q), IL-13 ligand(Q110R、C1055T)in Taiwanese children did not correlate to allergic disease, asthma , allergic rhinitis and patients who had asthma and allergic rhinitis. The polymorphism of IL-4 receptor(Q551R)was correlate to asthma(p = 0.0113), and I50V was associated with patients who had asthma and allergic rhinitis(p = 0.0338). Besides, IL-13 receptor(A1398G)was associated with allergic rhinitis. Combined with polymorphism and biochemical data, total IgE, eosinophil counts and serum IL-4 concentration were increased in allergic patients, asthma, allergic rhinitis and patients who had asthma and allergic rhinitis. The concentration of serum IL-13 were increased in asthma patients, but FEV1 did not decreased in the study.

壹、中文摘要 1
貳、英文摘要 3
參、前言 5
一、 過敏性疾病的定義 5
二、 過敏性疾病的致病機轉 6
三、 過敏性疾病的分類 6
1. 氣喘 6
2. 過敏性鼻炎 7
四、過敏性疾病與基因多型性的關係 8
五、研究動機 10
肆、 材料與方法 11
一、材料 11
1. 檢體來源 11
二、方法 13
1. 問卷調查 13
2. 萃取血漿 15
3. DNA純化 15
4. 聚合?連鎖反應(PCR--polymerase chain reaction) 17
(1)介白質-4聚合?連鎖反應(C589T、C33T) 17
(2)介白質-4受器聚合?連鎖反應(Arg576Gln【R576Q】、Gln551Arg【Q551R】、Ile50Val【I50V】) 17
(3)介白質-13聚合?連鎖反應(Gln110Arg【Q110R】、 C1055T) 18
(4)介白質-13受器聚合?連鎖反應(A1398G) 18
5. 限制片段長度多型性(RFLP--restriction fragment length polymorphism) 19
(1)介白質-4 C589T限制片斷長度多型性 19
(2)介白質-4 C33T限制片斷長度多型性 19
(3)介白質-4受器R576Q限制片斷長度多型性 20
(4)介白質-4受器Q551R限制片斷長度多型性 20
(5)介白質-4受器I50V限制片斷長度多型性 21
(6)介白質-13 Q110R限制片斷長度多型性 21
(7)介白質-13 C1055T限制片斷長度多型性 22
(8)介白質-13受器A1398G限制片斷長度多型性 22
6. 酵素結合免疫吸附分析(ELISA--enzyme-linked immunosorbent assay) 23
(1)人類血漿中介白質-4濃度分析 23
(2)人類血漿中介白質-13濃度分析 24
7. 統計方法 26
伍、結果 28
一、各個疾病組與對照組血清總IGE值、肺功能指標、血液嗜酸性球數目、介白質-4以及介白質-13濃度之差異 28
表一、各個疾病組與對照組之血清總IgE值的差異 30
表二、各個疾病組與對照組之肺功能指標的差異 31
表三、各個疾病組與對照組之血液嗜酸性球數目的差異 32
表四、各個疾病組與對照組之血清介白質-4濃度的差異 33
表五、各個疾病組與對照組之血清介白質-13濃度的差異 34
二、介白質-4基因C589T與過敏性疾病的關係 35
圖一、 介白質-4 C589T基因多型性之電泳凝膠分析圖 38
表六、C589T基因之對照組與各個疾病組性別的差異 39
表七、C589T基因多型性之對照組與各個疾病組的關係 40
表八、C589T基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、介白質-4、介白質-13濃度的關係 41
三、介白質-4基因C33T與過敏性疾病的關係 43
圖二、 介白質-4 C33T基因多型性之電泳凝膠分析圖 46
表九、C33T基因之對照組與各個疾病組性別的差異 47
表十、C33T基因多型性之對照組與各個疾病組的關係 48
表十一、C33T基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、介白質-4、介白質-13濃度的關係 49
四、介白質-4受器基因R576Q與過敏性疾病的關係 51
圖三、 介白質-4受器 R576Q基因多型性之電泳凝膠分析圖 54
表十二、R576Q基因之對照組與各個疾病組性別的差異 55
表十三、R576Q基因多型性之對照組與各個疾病組的關係 56
表十四、R576Q基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、介白質-4、介白質-13濃度的關係 57
五、介白質-4受器基因Q551R與過敏性疾病的關係 59
圖四、 介白質-4受器Q551R基因多型性之電泳凝膠分析圖 62
表十五、Q551R基因之對照組與各個疾病組性別的差異 63
表十六、Q551R基因多型性之對照組與各個疾病組的關係 64
表十七、Q551R 基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、介白質-4、介白質-13濃度的關係 65
六、介白質-4受器基因I50V與過敏性疾病的關係 67
圖五、 介白質-4受器 I50V基因多型性之電泳凝膠分析圖 70
表十八、I50V基因之對照組與各個疾病組性別的差異 71
表十九、I50V基因多型性之對照組與各個疾病組的關係 72
表二十、I50V基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、介白質-4、介白質-13濃度的關係 73
七、介白質-13基因Q110R與過敏性疾病的關係 75
圖六、 介白質-13 Q110R基因多型性之電泳凝膠分析圖 78
表二十一、Q110R基因之對照組與各個疾病組性別的差異 79
表二十二、Q110R基因多型性之對照組與各個疾病組的關係 80
表二十三、Q110R基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、介白質-4、介白質-13濃度的關係 81
八、介白質-13基因C1055T與過敏性疾病的關係 83
圖七、 介白質-13 C1055T基因多型性之電泳凝膠分析圖 86
表二十四、C1055T基因之對照組與各個疾病組性別的差異 87
表二十五、C1055T基因多型性之對照組與各個疾病組的關係 88
表二十六、C1055T基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、介白質-4、介白質-13濃度的關係 89
九、介白質-13受器基因A1398G與過敏性疾病的關係 91
圖八、 介白質-13受器A1398G基因多型性之電泳凝膠分析圖 94
表二十七、A1398G基因之對照組與各個疾病組性別的差異 95
表二十八、A1398G 基因多型性之對照組與各個疾病組的關係 96
表二十九、A1398G基因多型性與各個疾病組之血清總IgE值、肺功能指標、血液嗜酸性球數目、介白質-4、介白質-13濃度的關係 97
陸、討論 99
柒、參考文獻 103
捌、附表與附圖 109
附表一、介白質-4基因多型性序列引子 109
附表二、介白質-4 基因多型性聚合?連鎖反應條件 110
附表三、介白質-4受器基因多型性序列引子 111
附表四、介白質-4 受器基因多型性聚合?連鎖反應條件 112
附表五、介白質-13基因多型性序列引子 113
附表六、介白質-13基因多型性聚合?連鎖反應條件 113
附表七、介白質-13受器基因多型性序列引子 114
附表八、介白質-13受器基因多型性聚合?連鎖反應條件 114
附圖一、過敏性疾病發生機轉 115
附圖二、造成過敏性疾病(例如:氣喘)的主要原因 116

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