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主要公共卫生问题，但对遗传和环境因素对这个少数民族群体哮喘的发展和严重性的相对贡献知之甚少。该应用将检查波多黎各儿童中选定的遗传和环境因素与哮喘之间的关系。为此，我们将在康涅狄格州哈特福德（Hartford）招募500名波多黎各儿童（案例）和500名没有哮喘（对照组）的波多黎各儿童。为了开始确定影响波多黎各人哮喘的遗传因素，我们将在20个基因中基因型单核苷酸多态性（SNP）控制T-Helper（Th）1细胞，Th2细胞，TH2细胞和调节性T细胞（TREG）的发育和调控，并可能影响Puerto ricasans的病原体和严重性。 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嗜酸性粒细胞计数）在病例和对照中分别，c）哮喘严重程度。为了检查波多黎各人的室内过敏原暴露与哮喘表型之间的关系，我们将通过父母报告评估早期生命中的宠物（怀孕和/或生命的第一年），并测量参与儿童的家庭中六种过敏原（尘螨，蟑螂，猫，猫，狗，老鼠和小鼠）的水平。然后，我们将研究父母在早期生命中暴露于两只宠物（狗和猫）中的每一个的报告是否与哮喘（在所有受试者中）和特应特应降低（分别在病例和对照中）有关。此外，我们将检查当前暴露于高水平的室内过敏原（灰尘，蟑螂，狗，猫，老鼠和老鼠）是否与哮喘的严重程度和肺功能表型有关（减少FEV1和FEV1/VFVC，erage液的反应性增加，增加了在疾病中的erige液响应性，并减少了在疾病中的培训（E.G）和整个疾病（E.G）（E.G）（E.G. G. compopy（E.G）。 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.通过在波多黎各儿童中进行基于人群的病例对照协会研究，我们将开始解决一个重大而未研究的问题：遗传和环境因素对波多黎各人哮喘的发育和严重程度的影响。该应用将极大地有助于我们对哮喘的理解，尤其是在波多黎各人中。