Genes, Home Allergens and Asthma Puerto Rican Children

基因、家庭过敏原和波多黎各儿童哮喘

• 批准号: 7149515
• 负责人: Juan Carlos Celedon
• 金额: $ 77.88万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7149515
• 关键词: Puerto Rican; adolescence (12-20); allergens; asthma; atopy; blood tests; clinical research; eosinophil; gene environment interaction; genetic screening; genetic susceptibility; helper T lymphocyte; human genetic material tag; human subject; immunogenetics; middle childhood (6-11); respiratory disorder epidemiology; respiratory function; spirometry; suppressor T lymphocyte

DESCRIPTION (provided by applicant): Although asthma is a major public health problem in Puerto Ricans, little is known about the relative contribution of genetic and environmental factors to the development and severity of asthma in this ethnic minority group. This application will examine the relation between selected genetic and environmental factors and asthma in Puerto Rican children. To this end, we will recruit 500 Puerto Rican children with asthma (cases) and 500 Puerto Rican children without asthma (controls) in Hartford, Connecticut. To begin to identify genetic factors influencing asthma in Puerto Ricans, we will genotype single nucleotide polymorphisms (SNPs) in 20 genes that control the development and regulation of T-helper (Th)1 cells, Th2 cells, and regulatory T cells (Tregs) and may therefore influence the pathogenesis and severity of asthma in Puerto Ricans. We will then test for association between SNPs and haplotypes in these candidate genes and a) asthma (in all subjects), b) lung function phenotypes (airway responsiveness, spirometric measures of airflow obstruction [FEV1 and FEV1/FVC], and bronchodilator response) and atopy phenotypes (serum total and allergen-specific IgE, skin test reactivity to allergens, and peripheral blood eosinophil count) separately in cases and in controls, and c) asthma severity in cases. To examine the relation between indoor allergen exposure and asthma phenotypes in Puerto Ricans, we will assess exposure to pets in early life (during pregnancy and/or the first year of life) by parental report and measure the levels of six allergens (dust mite, cockroach, cat, dog, rat, and mouse) in the households of participating children. We will then examine whether parental report of exposure to each of two pets (dogs and cats) in early life is associated with reduced risks of asthma (in all subjects) and atopy (separately in cases and in controls). In addition, we will examine whether current exposure to high levels of indoor allergens (dust mite, cockroach, dog, cat, rat, and mouse) is associated with asthma severity and lung function phenotypes (reduced FEV1 and FEV1/VFVC, increased airway responsiveness, and reduced bronchodilator responsiveness) in cases, and with atopy phenotypes (e.g., increased serum total IgE) in cases and in controls. We will then examine whether SNPs and/or haplotypes in genes associated with asthma/asthma phenotypes interact with parental report of pet exposure in early life and/or current exposure to indoor allergens in influencing asthma and intermediate phenotypes of asthma (asthma severity, lung function phenotypes, and atopy phenotypes) in Puerto Rican children. By conducting a population-based case-control association study with adequate sample size in Puerto Rican children, we will start to address a significant yet unstudied problem: the influence of genetic and environmental factors on the development and severity of asthma in Puerto Ricans. This application will contribute greatly to our understanding of asthma in general, and among Puerto Ricans in particular.

描述（由申请人提供）：尽管哮喘是波多黎各人的一个主要公共卫生问题，但人们对遗传和环境因素对该少数民族哮喘的发展和严重程度的相对影响知之甚少。该应用程序将检查选定的遗传和环境因素与波多黎各儿童哮喘之间的关系。为此，我们将在康涅狄格州哈特福德招募 500 名患有哮喘的波多黎各儿童（病例）和 500 名没有哮喘的波多黎各儿童（对照）。为了开始确定影响波多黎各人哮喘的遗传因素，我们将对控制辅助 T 细胞 (Th)1 细胞、Th2 细胞和调节性 T 细胞 (Treg) 发育和调节的 20 个基因进行单核苷酸多态性 (SNP) 基因分型因此可能影响波多黎各人哮喘的发病机制和严重程度。然后，我们将测试这些候选基因中的 S​​NP 和单倍型之间的关联，以及 a) 哮喘（在所有受试者中），b) 肺功能表型（气道反应性、气流阻塞的肺活量测量 [FEV1 和 FEV1/FVC] 以及支气管扩张剂反应）和特应性表型（血清总 IgE 和过敏原特异性 IgE、过敏原皮试反应性和外周血嗜酸性粒细胞计数）病例和对照，以及 c) 病例哮喘严重程度。为了研究波多黎各人的室内过敏原暴露与哮喘表型之间的关系，我们将通过家长报告评估生命早期（怀孕期间和/或出生第一年）与宠物的接触情况，并测量六种过敏原（尘螨、尘螨、过敏原）的水平。蟑螂、猫、狗、大鼠和小鼠）参与儿童的家庭。然后，我们将检查父母在生命早期接触两只宠物（狗和猫）的报告是否与哮喘（在所有受试者中）和特应性（分别在病例和对照中）的风险降低相关。此外，我们将检查当前暴露于高水平的室内过敏原（尘螨、蟑螂、狗、猫、大鼠和小鼠）是否与哮喘严重程度和肺功能表型（FEV1 和 FEV1/VFVC 降低、气道反应性增加）相关和支气管扩张剂反应性降低），以及病例和对照中的特应性表型（例如，血清总 IgE 增加）。然后，我们将检查与哮喘/哮喘表型相关的基因中的 S​​NP 和/或单倍型是否与父母报告的早年接触宠物和/或当前接触​​室内过敏原的报告相互作用，从而影响哮喘和哮喘的中间表型（哮喘严重程度、肺功能）表型和特应性表型）波多黎各儿童。通过在波多黎各儿童中进行足够样本量的基于人群的病例对照关联研究，我们将开始解决一个重大但尚未研究的问题：遗传和环境因素对波多黎各人哮喘的发展和严重程度的影响。该应用程序将极大地有助于我们对哮喘的总体了解，特别是波多黎各人的哮喘。