Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan

Toshifumi Nomura, Masashi Akiyama, Aileen Sandilands, Ikue Nemoto-Hasebe, Kaori Sakai, Akari Nagasaki, Mitsuhito Ota, Hiroo Hata, Alan T. Evans, Colin N. A. Palmer, Hiroshi Shimizu, W. H. Irwin McLean

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    Abstract

    Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and shown to be major predisposing factors for atopic dermatitis ( AD). However, these studies have been mainly carried out in European populations. In early 2007, we identified two Oriental-specific FLG mutations in four Japanese families with IV and reported that filaggrin mutations were also significant predisposing factors for AD in Japan. However, the frequency of FLG mutations observed in our Japanese AD cohort (5.6%), was much lower than that seen in Europeans (up to 48%). Here, we studied a further seven Japanese families with IV and identified two additional nonsense mutations in FLG, S2889X, and S3296X. We found that more than 20% of patients in our Japanese AD case series carry FLG mutations, and there is significant statistical association between the four mutations and AD (chi(2) P = 8.4 x 10(-6); heterozygote odds ratio 7.57, 95% CI 2.84-23.03). These data emphasize that skin-barrier impairment due to reduced filaggrin expression plays an important role in the pathogenesis of AD and sheds further light on the genetic architecture of atopy in Japan.

    Original languageEnglish
    Pages (from-to)1436-1441
    Number of pages6
    JournalJournal of Investigative Dermatology
    Volume128
    Issue number6
    DOIs
    Publication statusPublished - Jun 2008

    Keywords

    • OF-FUNCTION MUTATIONS
    • GENE PREDISPOSE
    • RARE MUTATIONS
    • EARLY-ONSET
    • PHENOTYPES
    • PREVALENT
    • CHILDREN
    • BARRIER

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