Role of Prenatal Factors and Gene-Environment Interactions in Recurrent Wheezing

产前因素和基因-环境相互作用在反复喘息中的作用

基本信息

批准号：
8277873
负责人：
RAJESH KUMAR
金额：
$ 13.45万
依托单位：
LURIE CHILDREN'S HOSPITAL OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8277873
关键词：
Address Affect African American American Area Asthma Biological Birth Boston CCL2 gene CD14 gene Candidate Disease Gene Child Childhood Clinical Clinical Data Cohort Studies Collection Data Data Analyses Development Environment Epidemic Epidemiology Etiology Evaluation Extrinsic asthma Food Hypersensitivity Fostering Funding Future Genes Genetic Genetic Polymorphism Genetic Research Genetic Variation Genotype Goals Growth and Development function IL6 gene IL8 gene Individual Infection Infection of amniotic sac and membranes Inflammation Inflammatory Response Pathway Interleukin-2 K-Series Research Career Programs Lead Life Literature MMP8 gene MMP9 gene Mentors Minority Molecular Genetics Morbidity - disease rate National Institute of Child Health and Human Development National Institute of Environmental Health Sciences Natural Immunity Nested Case-Control Study Outcome Parents Pathway interactions Population Predisposition Premature Birth Prevalence Prevention Prospective Studies Public Health Recurrence Relative (related person)Reporting Research Research Design Research Infrastructure Research Personnel Resources Risk Risk Factors Role Sample Size Statistical Methods Stratification TLR4 gene Testing Tissue Inhibitor of Metalloproteinase-1 Training Tumor Necrosis Factor-alpha United States National Institutes of Health Variant Wheezing abstracting airway remodeling base case control cohort cost data acquisition design didactic education early childhood experience gene environment interaction genetic epidemiology high risk human TNF protein improved inner city lung injury postnatal premature prenatal prenatal risk factor prevent programs prospective respiratory response

项目摘要

DESCRIPTION (provided by applicant): This career development award will foster Dr. Kumar's development into an independent investigator in the area of genetic epidemiology of asthma and wheezing in admixed minority populations. Training will occur in a uniquely rich environment with mentoring from Dr. Xiaobin Wang, Dr. Robert Schleimer, and Dr. Carole Ober. External advisors include Dr. James Gern and Dr. Esteban Burchard. Training will include: didactic education in genetic epidemiology; practical experience in candidate gene and SNP selection, genotyping, genetic data acquisition and analysis; understanding of theoretical and statistical methods of GxE research; and developing expertise in inner city longitudinal cohort studies. These educational goals will be achieved in parallel to the project's specific aims as follows: Aim 1: We will evaluate the association of prematurity and chorioamnionitis with the subsequent development of early life wheezing in the Boston Birth Cohort. Aim 2: We will carry out a nested case control study to evaluate whether the associations observed in Aim 1 can be further modified by individual variants of candidate genes, after with adjustment for important covariates, multiple comparisons and population stratification. We will genotype common gene polymorphisms of the following groups of candidate genes: 1. Genes which are involved in the pathways of response to chorioamnionitis, including inflammatory response pathways and remodeling/modulation of lung injury pathways. 2. Immunoregulatory Innate Immunity Candidate Genes. The long term scientific goal of the project is to evaluate the extent to which prenatal factors are associated with disparities in recurrent early childhood wheezing, and whether these associations are modified by genetic variation. This under investigated area is of public health significance because African American inner city populations have much higher rates of wheezing and asthma ,and traditional risk factors do not explain these disparities. However, prematurity and specifically chorioamnionitis are differentially distributed along these same lines, and there is some biological rationale for the association of these two co-morbid epidemics. Elucidating these relationships may lead to improved understanding of disparities and prevention of wheezing morbidity. (End of Abstract)

描述（由申请人提供）：该职业发展奖将促进 Kumar 博士发展成为混合少数民族哮喘和喘息遗传流行病学领域的独立研究者。培训将在王晓斌博士、Robert Schleimer 博士和 Carole Ober 博士的指导下，在独特的丰富环境中进行。外部顾问包括 James Gern 博士和 Esteban Burchard 博士。培训将包括：遗传流行病学的教学；候选基因和SNP选择、基因分型、遗传数据采集和分析的实践经验；了解 GxE 研究的理论和统计方法；发展内城纵向队列研究的专业知识。这些教育目标将与该项目的具体目标并行实现，如下：目标 1：我们将评估早产和绒毛膜羊膜炎与波士顿出生队列中早期喘息的后续发展之间的关系。目标 2：我们将进行巢式病例对照研究，以评估在调整重要协变量、多重比较和群体分层后，目标 1 中观察到的关联是否可以通过候选基因的个体变异进一步修改。我们将对以下几组候选基因的常见基因多态性进行基因分型： 1.参与绒毛膜羊膜炎反应途径的基因，包括炎症反应途径和肺损伤途径的重塑/调节。 2. 免疫调节先天免疫候选基因。该项目的长期科学目标是评估产前因素与儿童早期反复喘息差异的关联程度，以及这些关联是否会因遗传变异而改变。这个正在调查的领域具有公共卫生意义，因为非裔美国人内城人口的喘息和哮喘发病率要高得多，而传统的危险因素并不能解释这些差异。然而，早产儿和特别是绒毛膜羊膜炎沿着相同的路线分布有差异，并且这两种共病流行病的关联存在一些生物学原理。阐明这些关系可能会提高对差异的理解并预防喘息发病率。（摘要完）