Determinants of asthma severity in Harlem (DASH)

描述（由申请人提供）：最近哮喘发病率上升， 死亡率对非裔美国人的影响不成比例。它 除了环境暴露，遗传易感性 造成这种差距的因素有很多。然而，人们对如何做到这一点知之甚少。 特定的遗传多态性，包括染色体5 q上的遗传多态性， 哮喘的发病机制。尽管特定多态性的流行 已知等位基因变体（allelic variants）在人群（population）中不同 分层），非裔美国人哮喘的遗传研究 典型地包括数量少和控制不充分。此外，委员会认为， 几乎没有关于免疫途径的信息， 哮喘的严重程度。我们的研究，DASH（哮喘的决定因素 严重性在哈莱姆），旨在建立特定基因型之间的联系， 变异体和表型标记，并阐明免疫途径， 与非裔美国人哮喘严重程度有关。DASH地址 实现我们长期目标的下一步，即，控制哮喘， 哈莱姆的非裔美国人。我们提出了一个病例对照研究， 居住在中部和西部哈莱姆的非裔美国人。 我们将检验我们的中心假设： 5g染色体改变了哮喘患者的疾病严重程度， 多态性和特异性T细胞应答表型在 有哮喘的人和没有哮喘的人研究计划将 解决以下具体目标：（1）定义表型和等位基因 非洲人中IL-4、IL-13和β 2肾上腺素受体基因的变异 美国哮喘个体（病例）和对照;（2）定义T细胞 非裔美国人哮喘患者的反应表型。DASH研究 代表了迄今为止最大的努力，研究遗传学， 哮喘在非洲裔美国人的人口;它试图阐明重要的 免疫机制（T细胞反应），有助于哮喘的严重程度。 此外，它使T细胞应答与特定等位基因的连锁成为可能。 变体。我们的方法是应用现代技术（单倍型分析; 免疫表型），以发展一个机制为基础的框架， 了解非洲裔美国人哮喘严重程度的基础途径 人口通过DASH研究收集的数据将阐明 新出现的哮喘管理方向的相关性，包括 药物遗传学策略，对于这个人群。潜在的公共卫生 对哮喘人群来说，这些益处是至关重要的。

DESCRIPTION (provided by applicant): The recent rise in asthma morbidity and mortality has impacted the African American population disproportionately. It is likely that in addition to environmental exposures, genetic susceptibility factors have contributed to this disparity. Little is known, however, about how specific genetic polymorphisms, including those on chromosome 5q, impact the pathogenesis of asthma. Though the prevalence of specific polymorphisms (allelic variants) is known to vary across populations (population stratification), genetic studies on asthma in African Americans have characteristically included small numbers, and inadequate controls. Moreover, there is almost no information about the immunological pathways that contribute to asthma severity in this population. Our study, DASH (Determinants of Asthma Severity in Harlem), seeks to establish the link between specific genotypic variants and phenotypic markers, and to elucidate immunological pathways that contribute to asthma severity in an African American population. DASH addresses the next step in reaching our long-range goal, i.e., to control asthma in the African American population of Harlem. We propose a case-control study of individuals of African American heritage, who live in Central and West Harlem. We will test our central hypothesis: Polymorphisms in candidate asthma genes on chromosome 5g modify disease severity in individuals who have asthma, and these polymorphisms and specific T cell response phenotypes differ between individuals who have asthma and those who do not. The research plan will address the following specific aims: (1) to define the phenotype and allelic variants of the IL-4, IL-13 and Beta2-adrenoreceptor genes among African American asthmatic individuals (cases) and controls; and (2) to define T cell response phenotypes among African Americans who have asthma. The DASH study represents the largest effort undertaken to date, to study the genetics of asthma in an African American population; and it seeks to elucidate important immunological mechanisms (T-cell responses) that contribute to asthma severity. Moreover, it enables the linkage of T-cell responses to specific allelic variants. Our approach is to apply modern technologies (haplotype analysis; immunophenotyping) toward development of a mechanism-based framework for understanding pathways that underlie asthma severity in the African American population. The data collected through the DASH study will elucidate the relevance of emerging directions for asthma management, including pharmacogenetic strategies, for this population. The potential public health benefits are critical for the asthmatic population in general.