臺灣博碩士論文加值系統

為了探討氣喘之環境因素及遺傳特性，本研究分成三部份來進行，第一部份是以高屏地區11-16歲國中學生為對象，分析室內室外環境因素與氣喘之相關性；第二部份則探討氣喘學童與家族中成員（祖父母、父母、兄弟姊妹）氣喘病史之聚集性，且進一步利用孟德爾分離分析探討氣喘之遺傳模式；第三部份則針對三種氣喘候選基因（Candidate genes）-TNFa、TNF-b（Lymphotoxin）及IgE high affinity receptor（FceRIb）進行基因多形性分析，以了解人類基因多形性是否與氣喘及異位性疾病產生相關。
所得結果如下:
（一）由1995年10月至1996年6月收集11至16歲165,173位國中學童，進行大規模橫斷性研究，來探討高屏地區室內、室外空氣污染與學童氣喘之相關。每一位學生與其父母皆要完成兒童氣喘及過敏國際研究（ISAAC）之影帶及標準問卷。內容包括有哮喘（wheezing）及過敏之各種症狀，以及二手煙及人口學變項等。
在控制了干擾因子後，學童有抽煙習慣者及暴露於二手煙都有較高氣喘危險性，其危險對比值分別為1.29（95﹪CI=1.17-1.42），1.08（95﹪CI=1.05-1.12）。此外研究也發現室外空氣污染與學童氣喘亦有顯著相關，校正干擾因子後，總懸浮微粒、二氧化氮、一氧化碳、臭氧、落塵量皆與氣喘具有顯著相關。本研究以社區為基礎，普查率高達96.9﹪，因此，在樣本選擇上幾乎無選擇性偏差，結果顯示二手煙、室外高度空氣污染之長期暴露是學童氣喘之重要危險因子。
（二）雖然氣喘具有高度遺傳性，但由於受疾病異質性及環境因子之影響，所以遺傳模式仍然不明確。因此本研究進行分離分析研究並且調整環境因子影響後，分別探討調整過敏病史及無調整過敏病史之氣喘遺傳模式。
本研究收集227個三代家族，每個家族至少有一位有氣喘兒童，共有1990個樣本進入研究，進行分離分析，所控制之干擾因子有年齡、性別、抽煙習慣及二手煙暴露。分析結果，若將過敏病史及其他環境因子一起置入模式中，則隱性遺傳及共顯性遺傳之對偶基因模式則被接受，並且，與其他模式相較起來隱性遺傳模式之Akaike''s Information Criterion （AIC）之數值最小為1377.13，在族群中主要基因頻率大約是0.56 ± 0.04。且由研究顯示至少有一主要基因共同影響氣喘及異位性疾病。單一基因可解釋部分與異位性疾病相關之氣喘致病原因，因此認為隱性遺傳之多基因/多因子（包括基因與環境因素共同作用）之遺傳模式為氣喘重要致病機轉。
（三）氣喘被認為是一種多基因/多因子遺傳因子與環境因素共同作用的慢性疾病，目前已有許多候選基因被認為與氣喘之致病機轉有關。本研究則將探討TNFa-308，LTaNcoI及FceRIb-gly237glu三種基因之多形性與氣喘之相關。
研究結果發現, 分析三種基因多形性在氣喘與健康對照兩組分佈頻率，發現LTaNcoI 及TNFa-308無顯著差異，但是FceRIb-gly237glu之變異率達顯著意義且危險對比值為2.80（95﹪信賴區間=1.14-6.87）。但若依照過敏有無加以分組，則發現過敏性氣喘較非過敏性對照者有顯著較高FceRIb-gly237glu變異率，危險對比值分別為3.58（95﹪CI=1.08-11.9）。而TNFa-308與LTaNcoI變異率則在各組間則無顯著差異。
此外，FceRIb-gly237glu，TNFa-308，LTaNcoI與高濃度IgE抗體（>1000kU/l）、灰塵、塵瞞及蟑螂特異性IgE過敏原抗體均未達顯著相關。若進行基因與基因多形性交互作用分析，則發現TNFa-308與FceRIb兩者同時有變異時則氣喘之危險對比值為2.79（95﹪CI=0.44-17.7），但仍未達顯著意義。

This study was divided into three parts to explore the associations between asthma and environmental factors and genetic components. The first part was to estimate the contribution of indoor and outdoor air pollution to the one year prevalence of adolescent asthma after taking personal susceptibility and other potential risk factors. The second part was to explore the family aggregation of asthma and inheritance component by segregation analysis. The third part was to assess the association between asthma and the polymorphisms of three candidate genes, and to determine the involvement of the TNFa, TNFb and FceRIb genes in the genetic determination of asthma.
The results were followings:
（1）A large-scaled cross-sectional study was conducted among 165,173 junior high school students aged 11 to 16 yrs in Kaohsiung and Pintong areas in Taiwan, from October 1995 to June 1996. Each student and his/her parents participating in the study completed a video and a written International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire about symptoms of wheezing and allergies, passive smoking, and demographic variables.
After adjusting for potential confounders, adolescents exposed to cigarette smoking (odds ratio=1.29, 95% confidence interval(CI) 1.17-1.42) and environmental tobacco smoke(ETS) (odds ratio=1.08, 95% confidence interval : 1.05-1.12) were found to have a higher risk of asthma. Total suspended particulates, nitrogen dioxide, carbon monoxide, ozone and airborne dust particles all displayed an independent association with asthma, respectively, after controlling for potential confound variables.
There were no selection biases in this community-based study, which provides evidence that passive smoking and long term, high average outdoor air pollution are independent risk factors of asthma.
(2) Although asthma has a significant heritable component, the mode of inheritance remains controversial. Segregation analysis for asthma was performed with and without a history of atopic diseases (dermatitis and rhinitis) after adjusting for environmental factors. To investigate whether asthma may be inherited through a major gene with two alleles, the REGD program of the SAGE package was conducted in 1,990 individuals from 227 families with at least one asthmatic children.
When the variables of atopic disease and environmental factors were included in the model as covariates, the models for a two-allele gene with a recessive or codominant inheritance could not be rejected, and Akaike''s Information Criterion (AIC) was smaller (1377.13) for the recessive model than all the other models tested, assuming a major gene with a population frequency of 0.56±0.04. Under the assumptions of the applied segregation, at least one major gene exists which could be a gene involved also in allergy. However, the data suggest that a single locus gene explains only a portion of asthma cases that is related to the history of atopic diseases. We suggest that a polygenic /multifactorial (genetic and environmental factors) influence with a recessive component inheritance may be involved in the pathogenesis of asthma.
（3）Asthma is a chronic disease which interact by genes and environmental factors. Some candidate genes are involved in the etiology of asthma. The study aim was to assess the association between asthma and the polymorphisms of TNFa-308, LTaNcoI and FceRIb-gly237glu. There are no differences between the asthma and non-asthma of polymorphisms of TNFa-308, LTaNcoI. The FceRIb-gly237glu mutant rate of asthma children was significantly higher than that of non-asthma children.
Asthma children（<18year old）and atopic asthma were found to have a higher risk of the FceRIb mutant with odd ratios 2.8（95﹪CI=1.14-6.87）and 3.58 (95%CI=1.08-11.9), respectively. But children exposed to home dust, mite and cockroach weren''t associated with the mutants of three genes. There are no significantly interaction effect between the mutants of genes on asthma.

封面
目錄
總摘要
第一章 前言
第二章 文獻回顧
第一節 氣喘的定義與診斷
第二節 氣喘的盛行率與發生率
第三節 氣喘人口學因素
第四節 氣喘環境因素
第五節 氣喘遺傳因素
附圖１ 氣喘之環境與基因致病機轉
附表１ 雙胞胎一致性研究
附表２ 氣喘與異位性疾病之候選基因（candidate gene）及染色體位置
參考文獻
第三章 室內室外空氣污染與青少年氣喘之相關研究
摘要
前言
材料與方法
結果
討論
參考文獻
圖表
第四章 氣喘家族之分離分析研究
摘要
前言
材料與方法
結果
討論
參考文獻
圖表
第五章 兒童氣喘與基因多形性相關分析00 TNFα0308， LTαNcoI，FcεRI0β
摘要
前言
材料與方法
結果
討論
參考文獻
第六章 討論與建議
參考文獻

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