Determinants of asthma severity in Harlem (DASH)

简介(申请人提供)：近年哮喘发病率上升及 死亡率对非裔美国人的影响不成比例。它 很可能除了环境暴露外，遗传易感性 造成这种差距的因素是多方面的。然而，人们对此知之甚少。 特定的遗传多态，包括染色体5q上的那些，会影响 哮喘的发病机制。尽管特定多态的流行 (等位基因变异)已知在不同的种群(种群)之间是不同的 分层)，关于非裔美国人哮喘的基因研究 其特点是人数较少，控制不充分。此外， 几乎没有关于免疫途径的信息。 这一人群中哮喘的严重程度。我们的研究，DASH(哮喘的决定因素 哈莱姆区的严重程度)，试图建立特定基因类型之间的联系 变异体和表型标志物，并阐明 导致非裔美国人哮喘的严重程度。破折号地址 实现我们的长期目标的下一步，即在 哈莱姆区的非裔美国人。我们建议进行一项病例对照研究 居住在哈莱姆区中部和西部的非裔美国人。 我们将检验我们的中心假设：候选哮喘基因的多态 染色体5g改变哮喘患者的疾病严重程度，而这些 多态和特异性T细胞反应表型不同于 有哮喘的人和没有哮喘的人。这项研究计划将 解决以下具体目标：(1)定义表型和等位基因 非洲人IL-4、IL-13和β2肾上腺素受体基因的变异 美国哮喘患者(病例)和对照组；(2)定义T细胞 患有哮喘的非裔美国人的反应表型。DASH研究 代表着迄今为止所做的最大努力，研究人类的遗传学 非洲裔美国人中的哮喘；它试图阐明重要的 导致哮喘严重程度的免疫机制(T细胞反应)。 此外，它还能够将T细胞对特定等位基因的反应联系起来 变种。我们的方法是应用现代技术(单倍型分析； 免疫表型)朝着基于机制的框架的发展 了解非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 针对这一人群的药物遗传策略。潜在的公共健康 对于哮喘患者来说，受益是至关重要的。

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.