Folliculin mutations are not associated with severe COPD
Michael H Cho1, Barbara J Klanderman, Augusto A Litonjua
1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital; and Harvard Medical School, Boston, MA, USA. remhc@channing.harvard.edu
BMC Medical Genetics
|January 1, 2009
Summary
Genetic variations in the folliculin (FLCN) gene are not a significant risk factor for developing severe chronic obstructive pulmonary disease (COPD). This study suggests distinct genetic causes for familial spontaneous pneumothorax and COPD.
Area of Science:
- Genetics
- Pulmonology
- Medical Research
Background:
- Folliculin (FLCN) mutations cause Birt-Hogg-Dubé syndrome, linked to pneumothorax, fibrofolliculomas, and kidney tumors.
- FLCN mutations are also found in familial spontaneous pneumothorax, and FLCN is hypothesized to play a role in emphysema due to pulmonary cysts in affected individuals.
Purpose of the Study:
- To investigate whether sequence variants in the FLCN gene are risk factors for severe chronic obstructive pulmonary disease (COPD).
Main Methods:
- Genotyped seven known FLCN mutations in 152 severe COPD probands.
- Performed bidirectional resequencing of FLCN exons in 41 probands, identifying 31 variants.
- Genotyped four identified FLCN variants in an independent cohort of 345 COPD subjects and 420 healthy male smokers.
Main Results:
- None of the seven previously reported FLCN mutations were found in severe COPD probands.
- No significant association was observed between the identified FLCN variants and the presence of COPD or emphysema-related phenotypes.
Conclusions:
- Genetic variations in the folliculin gene do not appear to be a major risk factor for severe COPD.
- Familial spontaneous pneumothorax and COPD likely have distinct genetic underpinnings, despite overlapping radiographic features.
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