GENE-ENVIRONMENT INTERACTIONS IN ASTHMA DEVELOPMENT

描述：哮喘在美国是一种主要的慢性疾病，也是最常见的 童年时期的慢性病。疾病控制中心估计， 1980至1994年间，哮喘患病率增加了75%， 西班牙裔和非裔美国人的发病率和死亡率不成比例。 遗传和环境因素是已知的重要风险因素。 哮喘的发展。基因内特定突变的相互作用与 特定环境因素(过敏原、真菌、环境烟草烟雾、 等)，然而人们对它知之甚少，尽管它在 了解哮喘的发展。在这场竞争性的更新中 我们寻求继续跟踪我们1002名儿童(549名)的申请 白人，268名西班牙裔，139名非裔美国人，以及46名其他人)，出生时入学，至 测试仔细量化环境因素的原始假设 (室内过敏原和环境烟草烟雾、ETS、暴露)是 与儿童哮喘发病率有关，其健康状况， 家族史、抗原特异性IgE状态、家庭环境和潜能 混杂因素得到了仔细的描述。我们已经跟踪了103名儿童 3年，508人，2年，391人，1年。在…的第一年 生命、喘息、持续咳嗽和呼吸短促的发作 分别为42%、49%和21%的儿童录制。到目前为止，180名儿童已经 据报道患有哮喘，拉美裔(波多黎各)和 非裔美国人。家族史和婴儿床垫尘螨水平 与哮喘风险呈正相关。在继续遵循 我们将评估哮喘发病的环境风险因素 直到7岁，并评估儿童的抗原特异性IgE状态。在这 应用我们提出的拓展前瞻性研究进行探索 哮喘发病风险中的基因-环境交互作用。我们的目标是 调查过敏原、ETS和其他空气污染物各自的作用 暴露，最初，几个候选基因之一-在 IL-4基因的启动子区域，这是一个被发现对癌症风险很重要的基因 过敏症和哮喘的发展。血液样本将被储存起来，这样，在 未来，可能会探索其他候选基因。我们广泛的角色描述 环境暴露和风险因素提供了一个独特的人群在 在哮喘和特应性疾病的发生发展中哪些基因-环境相互作用 进行检查，并可提供确定目标和 优先对遗传病患者进行环境干预 敏感度。

DESCRIPTION: Asthma is a major chronic disease in the U.S. and the most common chronic illness of childhood. The Centers for Disease Control estimate that the prevalence of asthma has increased 75 percent between 1980 and 1994, with disproportionate morbidity and mortality among Hispanic and African-Americans. Genetic and environmental factors are known to be important risk factors in asthma development. The interaction of specific mutations within genes with specific environmental factors (allergens, fungi, environmental tobacco smoke, etc.,), however, is poorly understood despite its crucial importance in understanding the development of asthma. In this competitive renewal application we seek to continue to follow our population of 1,002 children (549 White, 268 Hispanic, 139 African American, and 46 Other), enrolled at birth, to test the original hypothesis that carefully quantitated environmental factors (indoor allergens and environmental tobacco smoke, ETS, exposures) are associated with the incidence of asthma in children whose health status, familial history, antigen-specific IgE status, home environment, and potential confounders are carefully characterized. We have followed 103 of the children for 3 years, 508 for 2 years and 391 for one year. During the first year of life, episodes of wheeze, persistent cough, and shortness of breath were recorded for 42, 49 and 21 percent of the children. Thus far, 180 children have been reported with asthma, with higher rates for Hispanics (Puerto Rican) and African Americans. Familial history and infant mattress dust mite levels were positively associated with risk of asthma. In continuing to follow the population we will evaluate environmental risk factors for asthma development through age 7 and assess antigen specific IgE status of the children. In this application we are proposing to expand the prospective study to explore gene-environment interactions in the risk of asthma development. We aim to investigate the respective roles of allergens, ETS and other air contaminant exposures and, initially, one of several candidate genes - a polymorphism in the promoter region of the IL-4 gene, a gene found to be important for risk of atopy and asthma development. Blood samples will be banked so that, in the future, other candidate genes may be explored. Our extensive characterization of environmental exposures and risk factors provide a unique population within which gene-environment interactions in the development of asthma and atopy can be examined and may provide information necessary for targeting and prioritizing environmental interventions toward those with genetic susceptibility.