Epidemiology of Susceptibility to Airborne Particulates and Allergens to Asthma

哮喘空气颗粒物和过敏原易感性的流行病学

• 批准号: 7523262
• 负责人: GREGORY B DIETTE
• 金额: $ 13.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7523262
• 关键词: 12q; 17q; Adrenergic Receptor; Affect; African American; Age-Years; Airborne Particulate Matter; Alleles; Allergens; Antigens; Asthma; Attention; Baltimore; Biometry; Black race; Blood; Breathing; CD4 Positive T Lymphocytes; Candidate Disease Gene; Caucasians; Caucasoid Race; Cessation of life; Child; Childhood Asthma; Chromosomes; Chronic Disease; Cost Sharing; Cytokine Gene; Data; Development; Diagnosis; Dictyoptera; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiology; Ethnic group; Exposure to; First Degree Relative; Funding; Gene Cluster; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genomics; Genotype; Goals; Health education; Healthcare; Home environment; Hospitalization; Human; Human Genetics; Hypersensitivity; Individual; Inflammation; Interleukin-13; Interleukin-4; Knowledge; Minority; Modeling; Mus; Numbers; Particulate; Particulate Matter; Pathogenesis; Patients; Pattern; Personal Satisfaction; Persons; Phenotype; Physiology; Population; Populations at Risk; Predisposition; Prevalence; Preventive; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonology; Recruitment Activity; Research; Research Design; Research Personnel; Resources; Risk; Severities; Socioeconomic Status; Source; Study Subject; Symptoms; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Twin Studies; United States; Work; allergen Bla g 1; base; chromosome 5q loss; clinical phenotype; cockroach allergen; comparative; cost; environmental intervention; gene environment interaction; human data; inner city; mortality; novel; programs; pulmonary function; racial and ethnic; receptor; response

Asthma affects more than 17 million people in the United States and African-Americans are significantly more likely than Caucasians to be diagnosed with asthma. Alarmingly, asthma-related hospitalization and mortality in African Americans are also high. Key environmental factors, particularly those found indoors which have been shown to have relevance to pathogenesis of asthma, include allergens such as cockroach (Bla g 1) and airborne particulate matter (PM). These exposures are especially common in urban environments, where many affected African-Americans reside. Twin studies and studies of first-degree relatives of asthmatic individuals, that were not restricted to African-Americans, indicate a genetic component in the risk for asthma. Evidence supports the hypothesis that key genes may reside on chromosomes 5q, 12q and 17q but little is known about allelic variants of these candidate asthma genes in African Americans. The proposed study will examine the genetic basis of asthma in African-Americans with specific attention to genetic modifiers involved in the enhanced susceptibility of certain patients to airborne particulate matter and antigens. Our strategy is to employ high-throughput genomic technologies to examine the (i) patterns of gene expression to identify candidate genes and (ii) the genetic basis for polymorphisms in genes which explain susceptibility to PM in an inner city African-American population with asthma. Vital assets in this work include the tremendous efficiencies gained from working with populations of 900 African-American subjects who have been, or will be, recruited by studies funded separately, including approximately 400 subjects from the NIEHS/EPA funded Center for Childhood Asthma in the Urban Environment and 624 subjects from the Baltimore Asthma Severity Study (BASS) study. Other key resources that provide substantial leverage of resources, include the Microarray facilities and Genotyping cores that are resources of the NHLBI-funded Programs for Genomics Applications (PI: Garcia), including sharing of costs of microarray chips and supplies. The following specific aims are supported by the proposed study: Aim #1. To obtain and prioritize candidate genes for susceptibility to airborne particulate matter through gene expression profiling in human CD4+ T-lymphocytes. Aim #2. To identify polymorphisms in candidate genes associated with susceptibility to PM exposure in asthma and with asthma severity. Aim #3. To identify polymorphisms in candidate genes associated with an interactive effect of cockroach allergen and PM10 exposures on asthma severity.

哮喘在美国影响超过1700万人，而非裔美国人比高加索人被诊断出患有哮喘的可能性更大。令人震惊的是，非裔美国人与哮喘有关的住院和死亡率也很高。关键的环境因素，尤其是那些在室内发现的因素 与哮喘的发病机理有关，包括过敏原（例如蟑螂（BLA G 1）和空气颗粒物（PM）。在许多影响非裔美国人居住的城市环境中，这些暴露尤其普遍。 不限于非裔美国人的哮喘患者的一级亲戚的双重研究和研究表明哮喘风险的遗传成分。证据支持以下假设：关键基因可能存在于5q，12q和17q的染色体上，但对非裔美国人这些候选哮喘基因的等位基因变体知之甚少。拟议的研究将检查具有特定特异性的非裔美国人哮喘的遗传基础 注意某些患者对空气颗粒物和抗原的敏感性提高的遗传修饰剂。我们的策略是利用高通量基因组技术来检查基因表达的（i）模式以鉴定候选基因，以及（ii）基因中多态性的遗传基础，这些基因的遗传基础解释了对哮喘内部非裔美国人内部的非裔美国人人口中对PM的敏感性。 Vital assets in this work include the tremendous efficiencies gained from working with populations of 900 African-American subjects who have been, or will be, recruited by studies funded separately, including approximately 400 subjects from the NIEHS/EPA funded Center for Childhood Asthma in the Urban Environment and 624 subjects from the Baltimore Asthma Severity Study (BASS) study.提供大量资源杠杆作用的其他关键资源包括微阵列设施和基因分型核心，这些设施是NHLBI资助的基因组学应用程序（PI：GARCIA）的资源，包括分享微阵列芯片和供应成本的成本。拟议的研究支持以下具体目标： 目标＃1。通过人CD4+ T淋巴细胞中的基因表达分析获得并确定候选基因对空气颗粒物的敏感性。 目标＃2。确定与哮喘和哮喘严重程度中PM暴露相关的候选基因中的多态性。 目标＃3。确定与蟑螂过敏原和PM10暴露对哮喘严重程度的候选基因中的多态性。