Genetic & Environmental Risk Factors in Asthma Severity

遗传

基本信息

批准号：
6770987
负责人：
Brian P Leaderer
金额：
$ 44.47万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-09 至 2006-05-31
项目状态：
已结题

项目摘要

Over the past two decades asthma morbidity among children has increased dramatically, with disproportionate morbidity among Hispanic and African-Americans. Environmental factors (allergens, fungi, environmental tobacco smoke, air contaminants, cold air, etc.) are known to be associated with asthma severity in children. More recently genetic factors have been proposed as important determinants in the severity of asthma. The interaction of specific mutations within genes with specific environmental factors, however, is poorly understood despite its crucial importance in understanding asthma severity. In this application we seek to expand our asthma severity study to examine the gene-environment interactions in modifying asthma severity. The asthmatic children (14 percent Black, 27 percent Hispanic, 55 percent, Caucasian, 4 percent Other and 16 percent of mothers with an education level of less than 12 years of schooling) are currently being followed to test the hypothesis that carefully quantified indoor allergen exposures (house dust mite, cat, dog, cockroach and fungi) and air contaminant exposures (environmental tobacco smoke, nitrogen dioxide, nitrous acid, ozone, fine particle mass and pollen) are associated with asthma severity (daily respiratory symptoms, medication use, and utilization of health care services and lung function) in a population of 1,002 physician diagnosed asthmatic children between 5 and 12 years of age whose health status familial history, home environment, and potential confounders are carefully characterized. In this application we will investigate the respective roles of allergens, ETS and other air contaminant exposures and the presence of polymorphisms in the beta2 adrenergic receptor (Arg 16-Gly or Gln27-Glu) and in the promoter region of the IL-4 gene, particularly the TT polymorphism, in asthma severity while controlling for allergic status of the child. Although several candidate genes have been identified as potential genetic determinants of asthma severity, we chose beta2-AR and IL-4 polymorphisms as the initial genes to examine in this population because they have been linked to asthma severity. By collecting and storing blood samples, other candidate genes could be examined, as they are prioritized. Our extensive characterization of environmental exposures and risk factors for a large diverse population of asthmatic children, provide a unique population within which gene-environment interactions in the severity of asthma can be examined. This study will provide a basis to prioritizing environmental interventions to reduce asthma morbidity in children.

在过去的二十年中，儿童的哮喘发病率急剧增加，西班牙裔和非裔美国人的发病率不成比例。已知环境因素（过敏原，真菌，环境烟草烟雾，空气污染物，冷空气等）与儿童的哮喘严重程度有关。最近，已经提出了遗传因素是哮喘严重程度的重要决定因素。然而，基因中特定突变与特定环境因素的相互作用尚不清楚，尽管它在理解哮喘严重程度中至关重要。在此应用中，我们试图扩大我们的哮喘严重性研究，以检查改变哮喘严重程度的基因环境相互作用。目前正在遵循哮喘儿童（14％的黑人，27％的西班牙裔，55％，高加索人，4％和16％的教育水平不到12年的母亲），目前正在遵循以下量化的假设暴露量（房屋尘螨，猫，狗，蟑螂和真菌）和空气污染物暴露（环境烟草烟雾，氮二氧化氮，一硝酸，臭氧，细颗粒质量和花粉）与哮喘（每日呼吸症状，药物使用，使用，使用，使用，使用，使用，使用，颗粒质量和花粉）在1,002名医生中，医疗保健服务和肺功能的利用）被诊断为5至12岁之间的哮喘儿童，其健康状况家庭历史，家庭环境和潜在的混杂因素是仔细特征的。在此应用中，我们将研究过敏原，ETS和其他空气污染物暴露的作用，以及在beta2肾上腺素能受体（ARG 16-GLY或GLN27-GLU）以及IL-4基因的启动子区域中的多态性的存在，以及IL-4基因的启动子区域尤其是TT多态性，在控制儿童过敏状态的同时，哮喘的严重程度。尽管已经将几个候选基因确定为哮喘严重程度的潜在遗传决定因素，但我们选择beta2-ar和IL-4多态性作为在该人群中检查的最初基因，因为它们与哮喘的严重程度有关。通过收集和储存血样，可以通过优先考虑其他候选基因。我们对大量哮喘儿童人群的环境暴露和危险因素的广泛表征提供了独特的人群，可以检查基因环境的相互作用，从而可以检查哮喘的严重性。这项研究将为确定环境干预措施的优先级以减少儿童的哮喘发病率提供基础。