Gene by Environment Interactions in Asthma and Allergy

描述（由申请人提供）：哮喘和过敏是儿童最常见的慢性疾病，在西方国家的患病率持续增加。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起着重要作用。最近的研究表明，在生命早期接触动物可以预防哮喘和过敏，并且认为内毒素暴露介导了这种效应。内毒素由革兰氏阴性菌外膜的可溶性脂多糖（LPS）片段组成。据推测，内毒素暴露可以防止哮喘和过敏性疾病的发展，这取决于剂量，时间和个体的遗传学。内毒素首先被先天性免疫系统的组分感知和识别，然后引发级联反应，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育很重要。本申请试图检查编码先天免疫系统组分的基因是否与哮喘和过敏的发展相关，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。研究设计将是一个候选基因病例对照研究，并将测试基因与环境的相互作用。这个应用程序将结合联合收割机的资源和数据，从两个出生队列：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，我们将增加病例和对照的数量，并能够利用以前收集的数据和标本。目前正在收集两个队列的遗传物质血液，并将从储存的冷冻房屋灰尘中测量内毒素。

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.