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  • Title: Promoter analysis and aberrant expression of the MUC5B gene in diffuse panbronchiolitis.
    Author: Kamio K, Matsushita I, Hijikata M, Kobashi Y, Tanaka G, Nakata K, Ishida T, Tokunaga K, Taguchi Y, Homma S, Nakata K, Azuma A, Kudoh S, Keicho N.
    Journal: Am J Respir Crit Care Med; 2005 May 01; 171(9):949-57. PubMed ID: 15709052.
    Abstract:
    Diffuse panbronchiolitis (DPB) is a chronic inflammatory airway disease predominantly affecting Asian populations. DPB is considered to be a complex genetic disease. Considering the mucous hypersecretion of the disease, we hypothesized that the transcriptional activity of mucin genes may be altered in DPB. We analyzed nucleotide sequences of regulatory region of six mucin genes--MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7--and detected their promoter polymorphisms. Among them, the insertion/deletion polymorphism identified in the MUC5B gene was significantly associated with the disease (p = 0.0001). Transcriptional activity observed in the three major promoter haplotypes corresponded to the strength of the disease association in which these haplotypes are involved. Immunohistochemistry of the lung tissues of DPB revealed that MUC5B was abundantly expressed not only in bronchial glands but also in increased numbers of goblet cells on the bronchial surface, where MUC5AC is predominant and MUC5B expression is generally scarce in the normal lung. Marked mucous hypersecretion observed in DPB may be partly explained by increased and aberrant expression of MUC5B. The possible involvement of MUC5B gene in DPB was demonstrated. A further role of the MUC5B polymorphism in its pathogenesis should be studied in the future.
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