This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality. 1 Cigarette smoking is the major environmental risk factor for the development of COPD; however, considerable variability in the effect of smoking exists. In addition to the risk from smoking, subjects with alpha 1-antitrypsin deficiency have a major genetic risk factor for COPD; other genetic risk factors have not been identified. The frequent development of COPD in individuals with alpha 1-antitrypsin deficiency has provided a foundation for the protease-antiprotease hypothesis for the pathogenesis of COPD and served as a model of a well-characterized monogenic genetic disease. However, many subjects with early-onset COPD are not alpha 1-antitrypsin deficient. COPD is likely a complex disease with multiple genetic and environmental influences. In the Boston Early-Onset COPD Study, Dr. Edwin Silverman's research group has identified 140 individuals with severe early-onset COPD, without severe AAT deficiency, and more than 800 of their relatives. They have found a significantly increased risk for airflow obstruction and chronic bronchitis compared to control subjects with similar smoking histories. Within early-onset COPD families, genome scan linkage analysis has been performed with short tandem repeat (STR) markers and have identified two regions of significant linkage and several other regions of suggestive linkage to COPD-related phenotypes. To identify the COPD genetic determinants within these linked chromosomal regions, Dr. Silverman has proposed to perform fine mapping with association analysis of SNPs located across these linkage regions. In order to find early-onset COPD susceptibility genes and to determine if those genetic determinants also influence COPD at later ages, DNA samples have been collected from several other populations: 1) National Emphysema Treatment Trial (NETT) participants, who have severe COPD at later ages than the Boston Early-Onset COPD Study probands (initial subject); 2) Normative Aging Study (NAS) male control subjects, who have normal spirometry despite substantial smoking histories; and 3) Nurses Health Study (NHS) female control subjects, who have significant smoking histories but have not been diagnosed with obstructive lung disease. Utilizing these four unique populations with case-control and family-based genetic epidemiological approaches provides an excellent opportunity to identify COPD susceptibility genes. The purpose of this study is to test the hypothesis that identifiable genetic factors, other than Alpha-1 Antitrypsin deficiency influence the development of COPD.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000082-44
Application #
7374659
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2005-12-01
Project End
2006-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
44
Fiscal Year
2006
Total Cost
$1,321
Indirect Cost
Name
University of Florida
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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