Gene by Environment Interactions in Asthma and Allergy

描述(申请人提供)：哮喘和过敏症是儿童最常见的慢性疾病，在西方国家的流行率继续上升。哮喘和其他过敏性疾病是复杂的疾病，环境暴露可能与遗传风险因素相互作用，在这些疾病的发展中发挥重要作用。最近的研究表明，在生命早期接触动物可能会预防哮喘和过敏，而内毒素接触被认为介导了这一效应。内毒素是由革兰氏阴性细菌外膜的可溶性脂多糖(LPS)片段组成。据推测，内毒素暴露可能会预防哮喘和过敏性疾病的发展，这取决于个人的剂量、时间和遗传。内毒素首先被天然免疫系统的组成部分感知和识别，然后引发一连串的反应，最终产生细胞因子和共刺激分子，这可能对指导适应性免疫系统的发展至关重要。这项应用旨在检查编码先天免疫系统组件的基因是否与哮喘和过敏的发展有关，以及内毒素是否在这些疾病的发展中与这些基因相互作用。研究设计将是候选基因病例对照研究，并将测试基因与环境的交互作用。这项应用将结合来自两个出生队列的资源和数据：波士顿家庭过敏原和哮喘研究和康涅狄格州儿童哮喘研究。在这样做时，我们将增加病例和控制措施的数量，并将能够利用以前收集的数据和样本。目前正在两个队列中收集遗传物质的血液，并将从储存的、冷冻的房屋灰尘中检测内毒素。

DESCRIPTION (provided by applicant): Asthma and allergies are the most common chronic diseases of childhood, and their prevalence in Western countries continues to increase. Asthma and other allergic diseases are complex diseases, and environmental exposures, likely interacting with genetic risk factors, play important roles in the development of these disorders. Recent studies have shown that exposure to animals early in life may protect against asthma and allergies, and it is thought that endotoxin exposure mediates this effect. Endotoxin is comprised of soluble lipopolysaccharide (LPS) fragments of the outer membrane of gram-negative bacteria. It is postulated that endotoxin exposure may prevent the development of asthma and allergic disease depending on dose, timing, and genetics of the individual. Endotoxin is first sensed and recognized by components of the innate immune system, which then sets off a cascade of reactions, culminating in production of cytokines and co-stimulatory molecules which may be important in directing the development of the adaptive immune system. This application seeks to examine whether genes encoding components of the innate immune system are associated with the development of asthma and allergies, and whether endotoxin interacts with these genes in the development of these disorders. The research design will be a candidate gene case-control study, and gene-by-environment interactions will be tested. This application will combine resources and data from two birth cohorts: the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. In doing so, we will increase the number of cases and controls, and will be able to make use of previously collected data and specimens. Blood for genetic material is currently being collected on the two cohorts, and endotoxin will be measured from stored, frozen house dust.