Genetic Susceptibility to Asthma and IndoorAir Pollution in Peru

描述（由申请人提供）：哮喘是一种流行病，不成比例地影响儿童，穷人和某些种族/族裔群体。拉美裔/西班牙裔是美国增长最快的少数民族人口，并且不成比例地受到哮喘发病率的影响。从1990年到2000年，在美国人口普查调查中，秘鲁人的人数增加了81%，秘鲁的哮喘患病率是世界上最高的国家之一。哮喘是一种复杂的疾病，哮喘的遗传风险和哮喘发病率可能会受到环境暴露的影响。室内环境尤其令人关注，因为大多数人大部分时间都在室内度过。这项应用的研究人员已经表明，高水平的室内暴露，包括颗粒物（PM）和二氧化氮（NO2），与更高的哮喘发病率独立相关，并且在秘鲁家庭中特别高。哮喘的负担归因于国内PM和NO2浓度的差异是巨大的，然而，并不是所有的儿童都容易受到污染物暴露的影响，个体之间存在很大的差异。这些研究结果表明，在哮喘的发展中，遗传易感性和环境暴露之间存在相互作用的可能性很大。为了解决遗传易感性对室内空气污染对哮喘的不利影响的作用这一关键问题，我们将在秘鲁的基础设施和正在进行的数据收集工作的基础上进行研究。我们提出了一项候选基因研究，以确定与哮喘及其相关性状（即，哮喘严重程度、肺功能、气道炎症）与秘鲁两个城市利马和通贝斯室内空气污染物暴露的关系。我们将优先考虑已发表的哮喘全基因组关联研究确定的候选基因，以及被认为与污染物暴露和哮喘相关的氧化应激途径中的候选基因。我们将在来自秘鲁利马（n= 1，400）的特征明确的哮喘病例和对照中，在来自秘鲁Tumbes（n=400）的哮喘病例和对照的第二个独立群体中交叉验证鉴定的关联。具体目标#1：确定秘鲁儿童哮喘相关基因。具体目标#2：确定哮喘的遗传风险是否受到室内空气污染物（PM，NO2）浓度的影响。我们期望确定哮喘的候选基因和相关的性状相关的一般人群，以及那些有助于差异哮喘发病率之间的个人在秘鲁。确定特别易受空气污染影响的人口亚群是一个重要目标，因为研究结果可用于确定最有可能从避免接触空气污染中受益的人群。

DESCRIPTION (provided by applicant): Asthma is an epidemic that disproportionately affects children, the poor and certain racial/ethnic groups. Latinos/Hispanics are the fastest growing minority population in the US and are disproportionately affected by asthma morbidity. From 1990 to 2000 there was an 81 percent increase in number of people that mark their ethnic origin as Peruvian on the US Census survey and the prevalence of asthma in Peru is among one of the highest in the world. Asthma is a complex disease and genetic risk for asthma and asthma morbidity may be modified by environmental exposures. The indoor environment is of particular concern as most people spend the majority of their time indoors. Investigators in this application have shown that high levels of indoor exposures, including particulate matter (PM) and nitrogen dioxide (NO2), are independently associated with greater asthma morbidity, and are particularly high in Peruvian homes. The burden of asthma attributable to differences in domestic PM and NO2 concentrations is substantial; however, not all children are susceptible to effects of pollutant exposure and a large variation in response exists between individuals. These findings suggest a strong possibility of an interaction between genetic predisposition and environmental exposure in the development of asthma. To address the critical questions of the role of genetic susceptibility to the adverse effects of indoor air pollution on asthma, we will build upon the infrastructure and ongoing data collection efforts in Peru. We propose a candidate gene study to identify genetic variants associated with asthma and its associated traits (i.e., asthma severity, pulmonary function, airway inflammation) in relation to indoor air pollutant exposure in two Peruvian cities, Lima and Tumbes. We will prioritize candidate genes identified by published genome-wide association studies for asthma as well as those in the oxidative stress pathway thought to be relevant to pollutant exposure and asthma. We will cross-validate associations identified in well characterized asthma cases and controls from Lima, Peru (n=1,400), in a second independent population of asthmatic cases and controls recruited from Tumbes, Peru (n=400). Specific Aim #1: To identify genes associated with asthma in children in Peru. Specific Aim #2: To determine if genetic risk for asthma is modified by indoor air pollutant (PM, NO2) concentrations. We anticipate identifying candidate genes for asthma and associated traits relevant to both the general population as well as those contributing to disparities in asthma morbidity among individuals in Peru. Identifying subgroups of the population who are particularly vulnerable to air pollution is an important objective, as the results can be used to identify people most likely to benefit from exposure avoidance.