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Published ahead of print on October 9, 2003, doi:10.1164/rccm.200304-559OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 180-186, (2004)
© 2004 American Thoracic Society

Polymorphism of Clara Cell 10-kD Protein Gene of Sarcoidosis

Takashi Ohchi, Noriharu Shijubo, Isao Kawabata, Shingo Ichimiya, Shin-ichiro Inomata, Akihiro Yamaguchi, Yoshifumi Umemori, Yoshihisa Itoh, Shosaku Abe, Yomei Hiraga and Noriyuki Sato

Third Department of Internal Medicine; Department of Pathology, Sapporo Medical University School of Medicine; Department of Respiratory Medicine, Sapporo Hospital, Hokkaido Railway Company, Sapporo; and Department of Laboratory Medicine, Asahikawa Medical College, Asahikawa, Japan

Correspondence and requests for reprints should be addressed to Noriharu Shijubo, M.D., Department of Respiratory Medicine, Sapporo Hospital, Hokkaido Railway Company, North-3, East-1, Chuo-ku, Sapporo, 060-0033 Japan. E-mail address: shijubo{at}jrsapporohosp.com

Clara cell 10-kD protein (CC10) exhibits potent antiinflammatory properties. G38A polymorphism was found in the CC10 gene. We investigated the genetic influence of the allele on the development of sarcoidosis using case control analysis in a Japanese population (265 sarcoidosis cases and 258 control subjects). The A allele frequency in sarcoidosis cases (45.1%) was significantly higher than healthy control subjects (34.9%, p = 0.0002). According to outcomes, we divided 223 patients with follow-up periods of 3 years or more into two subgroups (55 progressive and 168 regressive disease). The A allele frequency in patients with progressive disease was significantly higher than control subjects (odds ratio = 4.55; 95% confidence interval, 2.97–6.97; p < 0.0001), whereas that of regressive disease was not. The A/A genotypes had significantly lower bronchoalveolar lavage fluid CC10 levels than the G/G (nonsmokers, p = 0.0054, and smokers, p = 0.0045) and G/A genotypes (nonsmokers, p = 0.0022, and smokers, p = 0.0402). The reporter gene assay showed significantly lower reporter activities in the presence of interferon-{gamma} for the 38A construct than the 38G construct (p = 0.0177). The G38A polymorphism in the CC10 gene may influence protein expression and be associated with the development of progressive sarcoidosis.

Key Words: Clara cell 16-kD protein • Clara cell secretory protein • protein 1 • secretoglobin • uteroglobin




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