Epidemiology of Susceptibility to Airborne Particulates & Allergens to Asthma in

在美国，哮喘影响着超过1700万人，非洲裔美国人比白人更容易被诊断为哮喘。令人担忧的是，非洲裔美国人与哮喘相关的住院率和死亡率也很高。关键的环境因素，特别是那些在室内发现的， 与哮喘发病机制相关的过敏原包括蟑螂（Bla g 1）和空气中的颗粒物（PM）等过敏原。这些暴露在城市环境中特别常见，许多受影响的非洲裔美国人居住在那里。 双胞胎研究和对哮喘个体一级亲属的研究（不限于非洲裔美国人）表明，哮喘风险中存在遗传因素。证据支持这一假设，即关键基因可能位于染色体5 q，12 q和17 q，但对非洲裔美国人中这些候选哮喘基因的等位基因变体知之甚少。这项拟议中的研究将检查非裔美国人哮喘的遗传基础， 注意与某些患者对空气中颗粒物和抗原的敏感性增强有关的遗传修饰剂。我们的策略是采用高通量基因组学技术来研究（i）基因表达模式，以确定候选基因和（ii）基因多态性的遗传基础，解释了城市中心的非裔美国人哮喘人群对PM的易感性。这项工作的重要资产包括与900名非洲裔美国人受试者一起工作所获得的巨大效率，这些受试者已经或将要被单独资助的研究招募，其中包括来自NIEHS/EPA资助的城市环境中儿童哮喘中心的约400名受试者和来自巴尔的摩哮喘严重程度研究（BASS）研究的624名受试者。其他提供大量资源杠杆的关键资源包括微阵列设施和基因分型核心，它们是NHLBI资助的基因组学应用程序（PI：Garcia）的资源，包括微阵列芯片和用品的成本分摊。拟议的研究支持以下具体目标： 目标1。通过人CD 4 + T淋巴细胞基因表达谱分析，获得并优先考虑对空气颗粒物易感的候选基因。 目标2。确定与哮喘PM暴露易感性和哮喘严重程度相关的候选基因多态性。 目标3。鉴定与蟑螂变应原和PM10暴露对哮喘严重程度的交互作用相关的候选基因的多态性。

Asthma affects more than 17 million people in the United States and African-Americans are significantly more likely than Caucasians to be diagnosed with asthma. Alarmingly, asthma-related hospitalization and mortality in African Americans are also high. Key environmental factors, particularly those found indoors which have been shown to have relevance to pathogenesis of asthma, include allergens such as cockroach (Bla g 1) and airborne particulate matter (PM). These exposures are especially common in urban environments, where many affected African-Americans reside. Twin studies and studies of first-degree relatives of asthmatic individuals, that were not restricted to African-Americans, indicate a genetic component in the risk for asthma. Evidence supports the hypothesis that key genes may reside on chromosomes 5q, 12q and 17q but little is known about allelic variants of these candidate asthma genes in African Americans. The proposed study will examine the genetic basis of asthma in African-Americans with specific attention to genetic modifiers involved in the enhanced susceptibility of certain patients to airborne particulate matter and antigens. Our strategy is to employ high-throughput genomic technologies to examine the (i) patterns of gene expression to identify candidate genes and (ii) the genetic basis for polymorphisms in genes which explain susceptibility to PM in an inner city African-American population with asthma. Vital assets in this work include the tremendous efficiencies gained from working with populations of 900 African-American subjects who have been, or will be, recruited by studies funded separately, including approximately 400 subjects from the NIEHS/EPA funded Center for Childhood Asthma in the Urban Environment and 624 subjects from the Baltimore Asthma Severity Study (BASS) study. Other key resources that provide substantial leverage of resources, include the Microarray facilities and Genotyping cores that are resources of the NHLBI-funded Programs for Genomics Applications (PI: Garcia), including sharing of costs of microarray chips and supplies. The following specific aims are supported by the proposed study: Aim #1. To obtain and prioritize candidate genes for susceptibility to airborne particulate matter through gene expression profiling in human CD4+ T-lymphocytes. Aim #2. To identify polymorphisms in candidate genes associated with susceptibility to PM exposure in asthma and with asthma severity. Aim #3. To identify polymorphisms in candidate genes associated with an interactive effect of cockroach allergen and PM10 exposures on asthma severity.