In:
Respirology, Wiley, Vol. 13, No. 4 ( 2008-06), p. 498-504
Abstract:
Background and objective: Cathepsin S is involved in the pathogenesis of COPD in murine models overexpressing interferon (IFN)‐γ and IL‐13. It is widely accepted that genetic factors partly influence susceptibility to COPD; however, the association of genetic polymorphisms in the cathepsin S gene with COPD has not been reported previously. In this study, functional polymorphisms in the 5′‐flanking region of the human cathepsin S gene were identified and their association with COPD phenotypes was investigated. Methods: Genetic polymorphisms were detected by single strand conformation polymorphism analysis and direct sequencing. Genotypes and haplotypes were determined using amplification refractory mutation systems and single strand conformation polymorphism analysis. A promoter‐reporter assay was used to compare transcriptional activities between the haplotypes on stimulation with IFN‐γ. Haplotype analysis was performed on 204 smoking and 104 non‐smoking Japanese subjects. Results: Four novel polymorphisms were detected in the 5′‐flanking region and three major haplotypes were identified. The haplotypes were associated with distinct promoter activities on stimulation with IFN‐γ and there was a trend indicating that higher transcriptional activity was linked to less pulmonary emphysema. Conclusion: Novel functional polymorphisms were identified in the cathepsin S gene, which has a possible association with pulmonary emphysema in the Japanese population.
Type of Medium:
Online Resource
ISSN:
1323-7799
,
1440-1843
DOI:
10.1111/res.2008.13.issue-4
DOI:
10.1111/j.1440-1843.2008.01280.x
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
2010720-1
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