Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00018408
Status:
COMPLETED
Last Update Posted:
2009-01-21
First Post:
2001-07-03
Brief Title:
Genetic Mechanisms of Chronic Obstructive Pulmonary Disease COPD
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Genetic Mechanisms of Chronic Obstructive Pulmonary Disease
Status:
COMPLETED
Status Verified Date:
2004-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether genetic factors contribute to an individuals risk of developing obstructive lung disease from smoking cigarettes
Detailed Description:
Chronic obstructive pulmonary disease COPD is among the most important chronic diseases of adults It is the fourth leading cause of death in the US and affects more than 10 of the US population over age 55 COPD accounts for more than 25000 discharges annually from VA medical centers Cigarette smoking is the most important known modifiable cause of COPD yet only 15-20 of cigarette smokers develop clinically significant COPD We therefore hypothesize that genetic mechanisms determine susceptibility to the development of COPD The only genetic abnormality known to cause COPD is deficiency of the serine protease inhibitor 1-protease inhibitor which causes premature development of emphysema although it is implicated in fewer than 2 of COPD cases Several other genetic variants have been proposed as candidate causes of COPD however these have been identified on the basis of association studies in unrelated subjects which have considerable risk of ascertainment bias In the present study a sub-pair linkage approach will be utilized in COPD patients and their smoking siblings to identify genes which determine the risk of developing COPD The following are the short-term objectives of this study
1 Recruit a cohort of 400 probands with smoking-related COPD and their smoking siblings whether or not affected by COPD Affected subjects will be extensively characterized as to specific COPD phenotype using spirometry computed tomography and questionnaire data
2 Test the association of known genetic variants in candidate genes to the presence of COPD
3 For proposed candidate genes without known candidate polymorphisms use sib-pair linkage analysis to test polymorphic marker loci in close proximity to the candidate gene for evidence of linkage to COPD
4 Test for heterogeneity of linkage among different COPD phenotypes predominant emphysema versus predominant airway disease
The long-term objective of this research is the identification of specific genetic variants which confer risk for the development of COPD in smokers This will be achieved by means of fine mapping of the loci identified in objectives 3-4 above or in a subsequent genome scan involving the 400 sibling pairs identification of novel genetic variants at these loci and assessment of the functional significance of these variants and their relation to COPD in an independent sample of subjects
Recruitment of subjects for this project began in April 1999 At this time a total of 22 subjects 11 COPD patients and 11 first-degree relatives have been recruited and tested No adverse events have occurred A computerized methodology for quantitation of emphysema from CT scans has been developed and has demonstrated adequate DNA extraction from our blood samples Genotyping has been deferred pending the recruitment of 50 subjects
1 Recruit a cohort of 400 probands with smoking-related COPD and their smoking siblings whether or not affected by COPD Affected subjects will be extensively characterized as to specific COPD phenotype using spirometry computed tomography and questionnaire data
2 Test the association of known genetic variants in candidate genes to the presence of COPD
3 For proposed candidate genes without known candidate polymorphisms use sib-pair linkage analysis to test polymorphic marker loci in close proximity to the candidate gene for evidence of linkage to COPD
4 Test for heterogeneity of linkage among different COPD phenotypes predominant emphysema versus predominant airway disease
The long-term objective of this research is the identification of specific genetic variants which confer risk for the development of COPD in smokers This will be achieved by means of fine mapping of the loci identified in objectives 3-4 above or in a subsequent genome scan involving the 400 sibling pairs identification of novel genetic variants at these loci and assessment of the functional significance of these variants and their relation to COPD in an independent sample of subjects
Recruitment of subjects for this project began in April 1999 At this time a total of 22 subjects 11 COPD patients and 11 first-degree relatives have been recruited and tested No adverse events have occurred A computerized methodology for quantitation of emphysema from CT scans has been developed and has demonstrated adequate DNA extraction from our blood samples Genotyping has been deferred pending the recruitment of 50 subjects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None