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

• 批准号: 7868008
• 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
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7868008
• 关键词: Address; Affect; African American; American; Area; Asthma; Biological; Birth; Boston; CD14 gene; Candidate Disease Gene; Child; Childhood; Clinical; Clinical Data; Cohort Studies; Collection; Data; Development; Education; 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; Platelet Factor 4; Population; Predisposition; Premature Birth; Prevalence; Prevention; Prospective Studies; Public Health; Pulmonary Surfactant-Associated Protein D; 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; 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

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）：该职业发展奖将培养Kumar博士成为混合少数民族人群哮喘和喘息遗传流行病学领域的独立研究者。培训将在一个独特而丰富的环境中进行，由王晓斌博士、Robert Schleimer博士和Carole Ober博士指导。外部顾问包括James Gern博士和Esteban Burchard博士。培训将包括：遗传流行病学教学教育；在候选基因和SNP选择、基因分型、遗传数据采集和分析方面具有实践经验；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。这些教育目标将与项目的具体目标并行实现，具体目标如下：目标1：我们将评估波士顿出生队列中早产和绒毛膜羊膜炎与早期生命喘息后续发展的关系。目标2：我们将进行一项嵌套病例对照研究，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改变。我们将对以下候选基因组的常见基因多态性进行基因型分析：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在多大程度上与儿童早期复发性喘息的差异相关，以及这些关联是否会因遗传变异而改变。这一正在调查的地区对公共卫生具有重要意义，因为非裔美国人在市中心的人口中患喘息和哮喘的比例要高得多，而传统的风险因素并不能解释这些差异。然而，早产儿，特别是绒毛膜羊膜炎在这条线路上的分布是不同的，这两种合并症的流行之间存在一些生物学上的联系。阐明这些关系可能有助于提高对差异和预防喘息发病率的理解。（摘要结束）