Genetic Susceptibility to Asthma and IndoorAir Pollution in Peru

秘鲁哮喘和室内空气污染的遗传易感性

• 批准号: 7993198
• 负责人: Nadia N Hansel
• 金额: $ 59.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-07 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7993198
• 关键词: Address; Adverse effects; Affect; Air Pollutants; Air Pollution; Area; Asthma; Biometry; Candidate Disease Gene; Censuses; Child; Childhood; Childhood Asthma; Chronic Disease; Cities; Clinical assessments; Complex; Data Collection; Development; Disease; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiology; Erythroid; Ethnic Origin; Ethnic group; Funding; General Population; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Hispanics; Home environment; Hypersensitivity; Individual; Indoor Air Pollution; International; Latino; Measures; Minority; Morbidity - disease rate; Nitrogen Dioxide; Nuclear; Oxidative Stress; Oxidative Stress Pathway; Particulate Matter; Pathway interactions; Peru; Phenotype; Pollution; Population; Population Heterogeneity; Prevalence; Public Health; Publishing; Pulmonary Function Test/Forced Expiratory Volume 1; Qualifying; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Risk; Role; Severities; Single Nucleotide Polymorphism; Subgroup; Surveys; Symptoms; Testing; Time; United States National Institutes of Health; Variant; airway inflammation; base; case control; experience; gene environment interaction; genetic variant; genome wide association study; global health; international center; pollutant; public health relevance; pulmonary function; racial and ethnic; response; trait; validation studies

DESCRIPTION (provided by applicant): Asthma is an epidemic that disproportionately affects children, the poor and certain racial/ethnic groups. Latinos/Hispanics are the fastest growing minority population in the US and are disproportionately affected by asthma morbidity. From 1990 to 2000 there was an 81 percent increase in number of people that mark their ethnic origin as Peruvian on the US Census survey and the prevalence of asthma in Peru is among one of the highest in the world. Asthma is a complex disease and genetic risk for asthma and asthma morbidity may be modified by environmental exposures. The indoor environment is of particular concern as most people spend the majority of their time indoors. Investigators in this application have shown that high levels of indoor exposures, including particulate matter (PM) and nitrogen dioxide (NO2), are independently associated with greater asthma morbidity, and are particularly high in Peruvian homes. The burden of asthma attributable to differences in domestic PM and NO2 concentrations is substantial; however, not all children are susceptible to effects of pollutant exposure and a large variation in response exists between individuals. These findings suggest a strong possibility of an interaction between genetic predisposition and environmental exposure in the development of asthma. To address the critical questions of the role of genetic susceptibility to the adverse effects of indoor air pollution on asthma, we will build upon the infrastructure and ongoing data collection efforts in Peru. We propose a candidate gene study to identify genetic variants associated with asthma and its associated traits (i.e., asthma severity, pulmonary function, airway inflammation) in relation to indoor air pollutant exposure in two Peruvian cities, Lima and Tumbes. We will prioritize candidate genes identified by published genome-wide association studies for asthma as well as those in the oxidative stress pathway thought to be relevant to pollutant exposure and asthma. We will cross-validate associations identified in well characterized asthma cases and controls from Lima, Peru (n=1,400), in a second independent population of asthmatic cases and controls recruited from Tumbes, Peru (n=400). Specific Aim #1: To identify genes associated with asthma in children in Peru. Specific Aim #2: To determine if genetic risk for asthma is modified by indoor air pollutant (PM, NO2) concentrations. We anticipate identifying candidate genes for asthma and associated traits relevant to both the general population as well as those contributing to disparities in asthma morbidity among individuals in Peru. Identifying subgroups of the population who are particularly vulnerable to air pollution is an important objective, as the results can be used to identify people most likely to benefit from exposure avoidance. PUBLIC HEALTH RELEVANCE: Asthma is the most common chronic disease in children and over 300 million people suffer from asthma worldwide, suggesting a large public health burden. We anticipate identifying candidate genes for asthma and associated traits relevant to both the general population as well as those contributing to disparities in asthma morbidity among individuals in Peru. Identifying subgroups of the population who are particularly vulnerable to air pollution is an important objective, as the results can be used to identify people most likely to benefit from exposure avoidance.

描述（由申请人提供）：哮喘是一种流行病，严重影响儿童、穷人和某些种族/族裔群体。拉丁裔/西班牙裔是美国增长最快的少数民族人口，他们不成比例地受到哮喘发病率的影响。根据美国人口普查，从1990年到2000年，秘鲁人的数量增加了81%，秘鲁的哮喘患病率是世界上最高的之一。哮喘是一种复杂的疾病，哮喘的遗传风险和哮喘发病率可能因环境暴露而改变。室内环境尤其值得关注，因为大多数人大部分时间都在室内度过。该项目的研究人员已经表明，高水平的室内暴露，包括颗粒物（PM）和二氧化氮（NO2），与更高的哮喘发病率独立相关，秘鲁家庭的哮喘发病率尤其高。由国内PM和NO2浓度差异引起的哮喘负担是巨大的；然而，并非所有儿童都容易受到接触污染物的影响，个人之间的反应存在很大差异。这些发现表明，在哮喘的发展过程中，遗传易感性和环境暴露之间很可能存在相互作用。为了解决遗传易感性对室内空气污染对哮喘不利影响的作用这一关键问题，我们将以秘鲁的基础设施和正在进行的数据收集工作为基础。我们提出了一项候选基因研究，以确定与两个秘鲁城市利马和通贝斯室内空气污染物暴露相关的哮喘及其相关特征（即哮喘严重程度、肺功能、气道炎症）相关的遗传变异。我们将优先考虑已发表的哮喘全基因组关联研究确定的候选基因，以及那些在氧化应激途径中被认为与污染物暴露和哮喘相关的基因。我们将交叉验证在秘鲁利马（n= 1400）的哮喘病例和对照中发现的关联，以及从秘鲁Tumbes招募的哮喘病例和对照的第二个独立人群（n=400）。具体目标1：确定秘鲁儿童哮喘相关基因。具体目标2：确定哮喘的遗传风险是否受到室内空气污染物（PM, NO2）浓度的影响。我们预计确定候选基因哮喘和相关性状相关的一般人群，以及那些有助于在秘鲁个体之间的哮喘发病率差异。确定特别容易受到空气污染影响的人群是一个重要目标，因为研究结果可以用来确定最有可能从避免接触中受益的人群。