ASTHMA IN PUERTO RICAN CHILDREN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 哮喘是儿童最常见的慢性疾病，其发病率在全国和世界范围内都在上升。 哮喘是遗传易感性和环境因素（基因与环境相互作用）的组合的表达，这些因素是导致气道炎症反应的多种细胞、化学介质和神经通路之间复杂相互作用的结果。 本研究的目的是研究西班牙裔/波多黎各儿童哮喘的遗传学，特别是与γ/δ链相关的T淋巴细胞受体（TCR）（“TCR-γ/δ”）和与α/β链相关的TCR（“TCR-α，β”）的作用。 这项研究利用了通过哮喘管理计划（称为轻松呼吸）和基于家庭的三人设计（哮喘儿童，父母双方，无论是否做作）确定的哮喘儿童。 我们假设，与T淋巴细胞相关的染色体区域的一个子集有助于西班牙裔儿童的哮喘表型，这些联系将因哮喘的严重程度，支气管高反应性和萎缩而异。 我们还假设这些区域的变化与气道中T细胞的功能变化有关。 本研究的具体目的是：1）使用单核苷酸多态性（SNP）检测不同严重程度的西班牙裔哮喘儿童及其父母的脱氧核糖核酸（DNA）中与T淋巴细胞相关的2个基因位点，特别是TCR-δ和TCR-β基因。 2)检测这些SNP标记在位置候选基因中与哮喘表型的连锁/关联，具体而言，通过Easy Breathing确定的家族三人组中哮喘的存在、哮喘严重程度、支气管高反应性、总血清免疫球蛋白E（IgE）水平、一秒用力呼气量（FEV 1）和对常见吸入性过敏原的皮试反应性;和3）通过测量循环血液和鼻上皮细胞中的TCR-γ、δ和TCR-α、β细胞以及培养物中生长的鼻细胞的细胞因子谱来确定这些区域中的差异是否与T细胞功能的变化相关。 这项研究将开始，以解决这个复杂的基因与环境相互作用的遗传成分，并可能有助于解释特别高的哮喘患病率在某些种族群体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma is the most common, chronic disease of children with an incidence that is rising both nationally and worldwide. Asthma is the expression of a combination of genetic predisposition and environmental factors (gene-by-environment interaction) that are the result of a complex interaction between multiple cells, chemical mediators and neural pathways leading to an airway inflammatory response. The goals of this study are to investigate the genetics of asthma in Hispanic/Puerto Rican children and specifically the role of the T lymphocyte receptor (TCR) associated with the gamma/delta chain ("TCR-gamma/delta")and the TCR associated with the alpha/beta chain ("TCR-alpha, beta"). This study utilizes children identified with asthma through an asthma management program called Easy Breathing and a family based trio design (child with asthma, both parents regardless of affectation). We hypothesize that a subset of chromosomal regions associated with T lymphocytes contributes to the asthma phenotype in Hispanic children and that these linkages will vary by asthma severity, bronchial hyper-responsiveness and atropy. We also hypothesize that changes in these regions are associated with functional changes in T cells in the airways. The specific aims of the study are: 1) To examine deoxyribonucleic acid (DNA) from Hispanic children with asthma of varying severity and their parents for 2 gene loci associated with T lymphocytes-specifically, the TCR-delta and the TCR-beta genes using single nucleotide polymorphisms (SNPs). 2) To test these SNP markers in positional candidate genes for linkage/association with asthma phenotype, and specifically, presence of asthma, asthma severity, bronchial hyper-responsiveness, total serum immunoglobulin E (IgE) level, forced expired volume in one second (FEV1) and skin test reactivity to common aeroallergens in family trios identified through Easy Breathing; and 3) To determine whether differences in these regions are associated with changes in T cell function by measuring TCR-gamma, delta and TCR-alpha, beta cells in circulating blood and nasal epithelial cells and the cytokine profiles of nasal cells grown in culture. This study will begin to address the genetic component of this complex gene-by-environment interaction and may help to explain the especially high prevalence of asthma in certain ethnic groups.