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研究生:劉宜萍
研究生(外文):I-Ping Liu
論文名稱:Interleukin-4promoter基因多型性,霉斑或霉味及其交互作用與學童氣喘之相關性研究
論文名稱(外文):The Interleukin-4 promoter gene polymorphism, mold and their interaction in childhood asthma
指導教授:黃彬芳黃彬芳引用關係
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:職業安全衛生學系碩士班
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:117
中文關鍵詞:氣喘Interleukin-4 promote基因多型性霉斑霉味交互作用
外文關鍵詞:asthmaInterleukin-4 promotegene polymorphismmold odorvisible moldinteraction
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普遍認為Interleukin-4 (IL4)與氣喘有關,但截至目前探討IL-4 promoter基因多型性與學童氣喘間相關性之研究卻很少,不論是在台灣氣喘或健康的學童其IL-4 promoter的基因型在此兩者間的出現頻率是否不同?仍未被探討。
本研究分為兩個階段。第一階段為橫斷型研究,研究目的為1、了解客家、閩南、外省、原住民以及外籍配偶之子女,其氣喘盛行率的情形。2、評估可能影響孩童期間氣喘發展的環境危險因子。3、評估雙親患有異位性疾病是否是造成氣喘的另ㄧ項因子。4、探討學童氣喘中,所處的環境因子及雙親患有異位性疾病的獨立及交互作用;第二階段為配對型的病例對照研究,研究目的為5、了解居家霉斑或霉味是否為造成學童氣喘的危險因子。6、比較interkeukein-4 promoter 基因型於病例組與對照組間的差異。7、評估學童氣喘於居家霉斑或霉味與IL-4 promoter間獨立與交互作用。
首先,本研究調查之地區於台灣北部4所小學,並招募了1922位學童。本研究使用國際過敏性疾病標準化問卷(ISAAC-C)評估環境因子之獨立及交互作用,並以雙親是否患有異位性疾病作為遺傳因子進行分析。第二階段,進行配對的病例對照研究,病例組與對照組是從參與調查的學童中選取。此部份是以年齡及性別作為條件,進行1:2的配對,最後總共有188位氣喘學童及376位對照組。本研究以口腔黏膜細胞之DNA以聚合酶連鎖反應(polymerase chain reaction; PCR)及限制片段長度多型性(restriction fragment length polymorphism; RFLP)進行Interleukin-4(IL-4) promoter基因多型性分析,環境因子以家中是否有霉斑以及是否聞到發霉味道進行研究分析。
在橫斷型研究發現,儘管氣喘盛行率在客家人、閩南人、外省人、原住民間皆無顯著差異(p>0.05),但外籍配偶所生之子女較其他族群有較高的危險性患有氣喘。經由邏輯斯迴歸調整干擾因子後,雙親患有氣喘(調整後的暴露勝算比(aOR)=5.30,百分之九十五信賴區間(95%CI=3.45-8.15))以及家中有霉味(調整後的暴露勝算比(aOR)=1.60,百分之九十五信賴區間(95%CI=1.15-2.24))或家中有霉斑(調整後的暴露勝算比(aOR)=1.43,百分之九十五信賴區間(95%CI=1.04-1.96))。在進行雙親患有氣喘及暴露霉斑或霉味的交互作用中發現,雙親患有氣喘及暴露霉味的觀察值暴露勝算比(調整後的暴露勝算比(aOR)=8.98,百分之九十五信賴區間(95%CI=4.72-17.1));雙親患有氣喘及暴露霉斑的觀察值暴露勝算比(調整後的暴露勝算比(aOR)=8.31,百分之九十五信賴區間(95%CI=4.81-14.4))。雙親患有氣喘及暴露霉味的期望值暴露勝算比為5.31,雙親患有氣喘及暴露霉斑的期望值暴露勝算比為4.03。兩者觀察值的暴露勝算比皆高於期望值,因此有交互作用的關係。
在配對的病例對照研究中,氣喘與家中暴露霉斑(調整後的暴露勝算比(aOR)=1.66,百分之九十五信賴區間(95%CI=1.05-2.63))及霉味(調整後的暴露勝算比(aOR)=1.92,百分之九十五信賴區間(95%CI=1.25-2.95))有關。比較IL-4 promoter基因型,基因型CT與家中暴露霉斑(調整後的暴露勝算比(aOR)=2.43,百分之九十五信賴區間(95%CI=1.24-4.77))及霉味(調整後的暴露勝算比(aOR)=2.17,百分之九十五信賴區間(95%CI=1.07-4.41))比TT基因型沒暴露霉斑或霉味有顯著的危險性。
本研究結果建議雙親患有氣喘以及學童暴露居家霉斑或霉味與氣喘有關且雙親患有氣喘及學童暴露霉斑或霉味有交互作用的關係。在基因分析方面,本研究並未發現IL-4 promoter基因與學童氣喘有關。然而若學童基因型為CT且家中暴露霉斑及霉味者比學童其基因型為TT且無暴露霉斑或霉味者,有明顯增加氣喘的危險性。
There are lemitted assessed the association between gene
polymorphisms of interkeukein-4 (IL-4) promoter and childhood asthma. However, whether or not the frequency of IL-4 gene polymorphisms is different between asthmatic and normal children among Taiwanese school children remain unexplored.
The study was conducted in two stages. The objectives of cross-sectional study (stage I) were 1) to understand whether or not the distributions of childhood asthma are different among offsprings of
Haka, Taiwanese, Mainlander, Taiwan aborigines and foreign parents; 2) to assess the effects of environmental factors on development of asthma during childhood; 3) to assess parental atopy as predictor of asthma; 4) to evaluate independent and joint effects of the environmental factors and parental atopy on the development of childhood asthma. The matched-pairs case-controls study (stage II) was 5) to assess the effects of visible mold or mold older in dwellings on development of asthma during childhood; 6) to assess interkeukein-4 (IL4) promoter as predictor of asthma by comparing the prevalence of polymorphism of IL4 promoter between cases and controls; 7) to evaluate independent and joint effects of the visible mold or mold older in dwellings and IL-4 promoter on the development of childhood asthma.
First, we conducted a survey in northern Taiwan. We randomly selected 4 elementary schools and recruited 1,922 children. We used The International Study of Asthma and Allergies in Childhood (ISAAC-C) questionnaires to evaluate the independent and joint effects environment factors, and parental atopy as predictor of genetic factors on the development of childhood asthma. Second, we carried out a matched-paired case-control study. The cases and controls were selected from the participants of the survey. We applied 1 case to 2 controls
matching by age, sex. The final study population we included 188 cases of asthmatic children and 376 controls. The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays were performed by oral mucosa DNA to determine polymorphism of Interleukin-4(IL-4) promoter and two indicators of exposure including histories of presence if visible molds and perceived mold odor in the home.
In cross-sectional study, we found the children whose mother are foreigner had higher risk of asthma than others, although the prevalence of asthma among Haka, Taiwanese, Mainlander, Taiwan aborigines was no significant differences (p>0.05). In logistic regression adjusting for confounding, parental asthma (adjusted odds ratio(aOR)=5.30, 95%CI=3.45-8.15) and the present of mold odor(aOR=1.60, 95%CI=1.15-2.24) or visible mold in home (aOR=1.43, 95%CI=1.04-1.96) were independent determinants of asthma. We applied additive model to evaluate the join effect between parental asthma and mold problems in home. We found the observed joint effects of parental asthma and exposure to mold odor (aOR=8.98, 95%CI=4.72-17.1), parental asthma and exposure to visible mold (aOR=8.31, 95%CI=4.81-14.4).The expected joints of parental asthma and exposure to mold odor, the adjusted odds ratio is 5.31, parental asthma and exposure to visible mold the adjusted odds ratio is 4.03.The observed joint effects were higher than expected.
In matched paired case-control study, the risk of childhood asthma were associated with visible mold (adjusted odds ratio (aOR)=1.66, 95% confidence interval (CI)=1.05-2.63) and mold odor (aOR=1.92, 95%CI=1.25-2.95). Compared with the IL-4 promoter genotype, the genotype of CT had a significantly increased risk of childhood asthma with visible mold exposure (aOR=2.43, 95%CI=1.24-4.77) and mold odor (aOR=2.17, 95%CI=1.07-4.41) than the genotype of TT without presence of visible mold or mold older.
Our findings suggest that parental asthma and presence of visible mold or mold odor were associated with the risk of childhood asthma. There were strong the evidence on the interaction between parental asthma and children exposure to mold. In the genetic analysis, there were no apparent effect of IL-4 promoter gene on the development of childhood asthma. However, compared with participants carrying TT genotype with no presence of visible mold or mold odor, those who are genotype of CT with visible mold and mold odor had a significantly increased risk of asthma.
誌謝..............I
中文摘要.........III
Abstract..........VI
表目錄…….. XI
圖目錄…… XIV
第一章 緒論 1
第一節 研究背景 1
第二節 研究之重要性 4
第三節 研究目的 5
第二章 文獻探討 7
第一節 氣喘盛行率 7
第二節 氣喘概述 8
第三節 與氣喘相關的危險因子 9
第四節 Interleukein-4 promoter 基因與氣喘 14
第五節 Interleukein-4 promoter 基因與氣喘之研究現況 16
第三章 研究方法...19
第一節 研究設計 19
第二節 資料收集 20
第三節 研究對象 21
第四節 暴露評估 22
第五節 實驗方法 24
第六節 資料統計與分析 32
第四章 研究結果 35
第一節 大規模橫斷型研究分析結果 35
第二節 病例-對照研究之分析結果 44
第五章 討論 48
第一節 橫斷型研究 49
第二節 病例對照研究57
第六章 結論與建議 61
第一節 結論 61
第二節 研究限制 63
第三節 應用與建議 64
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