Genetic Mechanisms of Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by:
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00018408
First received: July 3, 2001
Last updated: January 20, 2009
Last verified: December 2004
  Purpose

The purpose of this study is to determine whether genetic factors contribute to an individuals risk of developing obstructive lung disease from smoking cigarettes.


Condition
Chronic Obstructive Lung Disease

Study Type: Observational
Study Design: Time Perspective: Retrospective
Official Title: Genetic Mechanisms of Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Study Start Date: October 1998
Estimated Study Completion Date: September 2001
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 U.S. and affects more than 10% of the U.S. population over age 55. COPD accounts for more than 25,000 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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  1. Age greater than or equal to 40 years
  2. Cigarette smoking greater than or equal to 30 pack years
  3. Obstructive Spirometry
  4. First degree relative with smoking history willing to participate
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00018408

Locations
United States, Massachusetts
VA Boston Healthcare System
Boston, Massachusetts, United States, 02130
Sponsors and Collaborators
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00018408     History of Changes
Other Study ID Numbers: CADE-ARCD1
Study First Received: July 3, 2001
Last Updated: January 20, 2009
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
COPD
Smoking

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 23, 2014