Functional Genomic Biomarkers in COPD

慢性阻塞性肺病的功能基因组生物标志物

• 批准号: 6789946
• 负责人: John J Reilly
• 金额: $ 55.32万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-23 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789946
• 关键词: biomarker; chronic obstructive pulmonary disease; clinical research; diagnosis design /evaluation; functional /structural genomics; genetic polymorphism; genetic susceptibility; human subject; patient oriented research; respiratory disorder diagnosis

DESCRIPTION (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) affects over 18 million Americans. It is clear that the major environmental risk factor for this debilitating syndrome is cigarette smoking. It is not clear, however, what factors are responsible for the fact that some smokers develop the disease while most do not. Studies of potential therapies have been hampered by the lack of easily measurable characteristics that predict the course of the disease. Most studies have used measures of lung function as a marker of disease activity. Such studies typically require large numbers of patients and an observation period of months to years. This application proposes studies to develop alternative biomarkers associated with COPD. The research proposed will develop a set of candidate biomarkers by utilizing expression array profiling to characterize gene expression patterns in lung tissue and peripheral blood associated with the presence of COPD. These candidates will then be assessed in studies performed in populations previously characterized for COPD-related phenotypes: the Boston Early Onset COPD Study and the Normative Aging Study. The initial studies will involve expressionprofiling in both lung tissue and peripheral blood in samples obtained from patients undergoing pulmonary resections at Brigham and Women's Hospital. Samples from 20 patients with airflow obstruction on spirometry and emphysema demonstrated on chest CT scans will be compared to samples from 20 matched control patients. State of the art bioinformatic analytic techniques will be used to analyze these data and develop a list of candidate biomarkers based on expression differences. Polymorphisms in the candidate genes will then be studied for genetic association in two characterized populations with different disease distributions. The Boston Early Onset COPD Study consists of patients who have been diagnosed at an early age with severe COPD and their family members. In contrast, the Normative Aging Study includes participants with a broad spectrum of COPD. Studies in these populations will be directed at establishing whether differences in gene expression or gene polymorphisms are associated with COPD. It is hoped that these markers will provide insight into disease pathogenesis and serve as outcome assessment parameters.

描述（由申请人提供）：