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研究生:林則成
研究生(外文):Che-Chen Lin
論文名稱:ICAM1基因多型性和環境菸草煙霧暴露與兒童氣喘的相關性
論文名稱(外文):ICAM1 Polymorphisms, Environmental Tobacco Smoke Exposure and Childhood Asthma
指導教授:李郁芬李郁芬引用關係
指導教授(外文):Yu-Fen Li
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:環境醫學研究所碩士班
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:66
中文關鍵詞:ICAM1環境菸草煙霧兒童氣喘
外文關鍵詞:ICAM1environment tobacco smokechildhood asthma
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背景:氣喘是一種多因性的慢性呼吸道疾病,無法以單一因子來解釋氣喘的發展,對於基因、環境因子與兩因子之間交互作用如何造成氣喘的發生仍然有很多需要探討。細胞間黏附分子1 (intercellular adhesion molecule 1,ICAM1)是發炎反應的重要因子,也被認為是氣喘的易感受基因。本研究目的是調查ICAM1基因中兩個單一核苷酸多型性(single nucleotide polymorphisms, SNPs) rs5491 (K56M, A/T)與rs5498 (K469E, A/G)對於孩童氣喘的影響,同時分析ICAM1基因與環境菸草煙霧暴露對於氣喘的交互作用。
材料與方法:本研究為採橫斷式研究方法,選定台灣宜蘭、台中與嘉義三區的國小學童於2006年4月至2008年4月進行問卷訪視,利用氣喘篩檢問卷以區分研究族群中的病例組與對照組,同時透過收集學童口腔細胞樣本為DNA的來源,並進行兩個ICAM1基因SNPs的基因型鑑定。排除拒絕提供孩童口腔細胞以及無法判定ICAM1中的任一個SNP的基因型者,本研究共納入771人作後續的資料分析。使用卡方檢定、邏輯斯迴歸了解ICAM1基因多型性、ICAM1單體型(haplotypes)和環境因子中環境菸草煙霧與兒童氣喘之間的關係。
結果:調整可能的干擾因子後,攜帶rs5491 AT或TT基因型者相較於攜帶AA基因型者有1.42倍氣喘風險(95% CI = 0.70-2.88);攜帶rs5498 AA或AG基因型者相對於攜帶GG基因型者有1.30倍的氣喘風險(95% CI = 0.56-3.03);rs5491與rs5498之間對於氣喘的交互作用未達統計顯著(交互作用p值 > 0.05)。單體型分析的結果顯示ICAM1對於氣喘無單體型效應(整合檢定p值 = 0.612)。環境菸草煙霧的暴露分別與ICAM1的兩個SNPs之間對於氣喘的發生具有交互作用雖未達統計顯著(2個SNPs與環境菸草煙霧暴露的交互作用p值皆 > 0.05),但可以觀察到在不同的環境菸草煙霧暴露下ICAM1的rs5491基因型對於氣喘有不同程度的影響。
結論:本篇研究是首篇針對台灣孩童族群的ICAM1基因多型性與氣喘的相關性研究,由我們的研究結果顯示ICAM1基因型和環境菸草煙霧的暴露對於孩童氣喘的發展可能扮演一個非常重要的角色。本研究結果可提供未來進行相關性研究或功能性研究的一個方向。
Background: Asthma is a chronic respiratory disease. It is still uncertain how genes, environmental factors, and their interaction are related to asthma occurrence, although several mechanisms have been proposed. Intercellular adhesion molecule-1(ICAM1) plays an important role in the inflammatory pathway, and is an asthma susceptibility gene. We investigated the role of two ICAM1 functional single nucleotide polymorphisms (SNPs) at codon 56 (K56M, rs5491, A/T) and codon 469 (K469E, rs5498, A/G) in childhood asthma, and examined the effect modification associated with children’s exposure status of environmental tobacco smoke (ETS).
Methods: We conducted a population-based cross-sectional study of elementary schools in Yilan, Taichung, and Chiayi during April 2006 and April 2008. We used structure questionnaire to definite case and control group in this study. After excluding individuals with missing genotypes on ICAM1 polymorphisms, 771 participants were included in the analyses. The associations between ICAM1 SNPs, ETS exposure, and asthma were estimated using logistic regression model with adjustments for confounders including gender, age, and school locations.
Results: After adjusting for confounders, the T allele of rs5491 (56M) was associated with a higher risk of asthma (OR = 1.42, 95% CI = 0.70-2.88); an individual carrying an AA or AG genotype at codon 469 was also at an increased risk of asthma (OR = 1.30, 95% CI = 0.56-3.03) compared to carrying an GG genotype. Our results revealed that there was no interaction between rs5491 and rs5498 (p-value for the interaction > 0.05) and no haplotype effect on asthma (p-value for global test = 0.612). The associations between rs5491, rs5498, and asthma were not statistically significantly modified by ETS exposure (p-value for interaction > 0.05 for both SNPs). However, our results suggested that ICAM1 rs5791 genotypes might have different effects on asthma by ETS exposure.
Conclusions: The present study was the first one to investigate the associations between ICAM1 gene and asthma in Taiwanese children. These findings suggest that the genetic variations in ICAM1 gene and ETS exposure may play important roles in the development of asthma in Taiwanese children. Our results also provide a direction for further studies on the association between ICAM1 gene polymorphisms, exposure of ETS, and childhood asthma.
中文摘要 I
ABSTRACT III
目錄 V
表目錄 VII
圖目錄 VIII
第一章 序論 1
第一節 研究背景與研究動機 1
第二節 研究目的 2
第三節 研究問題與研究假設 3
第四節 名詞界定 4
第二章 文獻探討 5
第一節 氣喘的定義、診斷與致病機轉 5
2-1-1 氣喘的定義 5
2-1-2 氣喘的診斷 6
2-1-3 氣喘的致病機轉 7
第二節 氣喘盛行率 9
2-2-1 台灣氣喘盛行率 9
2-2-2 他國氣喘盛行率 10
第三節 氣喘相關的空氣污染物 13
第四節 ICAM1基因介紹 14
第五節 ICAM1的基因與氣喘之相關性 17
第三章 研究方法 19
第一節 研究設計 19
第二節 研究對象 20
第三節 研究問卷設計與資料收集 21
第四節 樣本收集與基因型鑑定 24
3-4-1 口腔細胞的收集 24
3-4-2 DNA萃取與純化 24
3-4-3 基因型鑑定 25
第五節 資料分析 26
3-5-1 基本資料分析 26
3-5-2 哈溫平衡檢定 26
3-5-3 遺傳模式的選定 28
3-5-4 整合檢定(global test) 29
3-5-5 單體型估算 29
第四章 研究結果 30
第一節 研究族群特徵 30
第二節 人口學和環境因子與氣喘的相關性 38
第三節 ICAM1基因和氣喘的相關性與ICAM1基因-基因交互作用 44
第四節 ICAM1基因與環境菸草煙霧對氣喘的交互作用 49
第五章 討論 51
第一節 研究對象的特性 51
第二節 關於ICAM1基因的特性與對氣喘的影響 52
第三節 環境菸草煙霧暴露與ICAM1基因功能對於氣喘的影響 56
第四節 研究限制 57
第六章 結論與建議 60
第一節 結論 60
第二節 未來發展與建議 61
參考文獻 62
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