Genome screen for asthma and bronchial hyperresponsiveness: Interactions with passive smoke exposure
Genome screen for asthma and bronchial hyperresponsiveness: Interactions with passive smoke exposure
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DOI：
10.1016/j.jaci.2005.01.070
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发表时间：
2005-06-01
影响因子：
14.2
通讯作者：
Bleecker, ER
中科院分区：
文献类型：
--
作者：
Meyers, DA;Postma, DS;Bleecker, ER
背景：哮喘是一种常见的呼吸系统疾病，是遗传易感性和暴露于多种环境因素共同作用的结果。以父母吸烟为特征的被动吸烟暴露已被证明是过敏性和哮喘发展的一个危险因素。目的：我们试图对哮喘和支气管高反应性（BHR）进行全基因组连锁筛查，并确定儿童时期被动烟草烟雾暴露对遗传连锁研究结果的影响，以调查基因-环境相互作用。方法：对200个通过父母患有哮喘确定的家庭进行哮喘和BHR全基因组连锁筛查。对整个样本以及吸烟暴露家庭和非吸烟暴露家庭分别进行了分析。结果：对于哮喘和BHR，最有力的证据是在染色体3p和5q上观察到连锁。儿童暴露于被动吸烟的家庭提供了BHR与5q相关的证据（P < 0.001），但在两组家庭中都发现了与3p相关的证据。哮喘也观察到类似的结果。然而，与未暴露于烟雾的家庭相比，暴露于烟雾的家庭的后代患哮喘或BHR的频率没有观察到差异。结论：本研究的结果表明，易感基因对哮喘等常见疾病的影响可能并不明显，除非有适当的环境刺激暴露，如被动暴露于香烟烟雾。这种方法对哮喘易感基因的鉴定是有用的。
Background: Asthma is a common respiratory disease caused by the interaction of genetic susceptibility and exposure to various environmental factors. Passive smoke exposure, characterized by parental smoking, has been shown to be a risk factor for the development of atopy and asthma.Objective: We sought to perform a genome-wide linkage screen for asthma and bronchial hyperresponsiveness (BHR) and to determine the influence of passive tobacco smoke exposure during childhood on the results of genetic linkage studies to investigate gene-environment interactions.Methods: A genome-wide linkage screen for asthma and BHR was performed in 200 families ascertained through a parent with asthma. Analyses were performed separately for the entire sample and for the smoking-exposed and nonexposed families.Results: For asthma and BHR, the strongest evidence for linkage was observed for chromosomes 3p and 5q. The families in which the children were exposed to passive smoking accounted for the evidence for linkage of BHR to 5q (P < .001), but evidence for linkage to 3p was found in both sets of families. Similar results were observed for asthma. However, there was no observed difference in the frequency of asthma or BHR in the offspring from the smoke-exposed compared with the nonexposed families.Conclusion: The results from this study demonstrate that the influence of susceptibility genes for a common disease such as asthma might not be apparent unless there is the appropriate exposure to environmental stimuli, such as passive exposure to cigarette smoke. This approach should be useful for identification of asthma susceptibility genes.