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Common functional polymorphisms in the cathepsin S promoter in Japanese subjects: Possible contribution to pulmonary emphysema
Author(s) -
MINEMATSU Naoto,
NAKAMURA Hidetoshi,
FURUUCHI Momoyo,
NAKAJIMA Takahiro,
TAKAHASHI Saeko,
TSUJIMURA Shuko,
TATENO Hiroki,
ISHIZAKA Akitoshi
Publication year - 2008
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2008.01280.x
Subject(s) - haplotype , genetics , genotype , promoter , gene , pathogenesis , copd , cathepsin s , medicine , biology , cathepsin , microbiology and biotechnology , immunology , gene expression , enzyme , biochemistry
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.