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

J Invest Dermatol. 2008 Jun;128(6):1436-41. doi: 10.1038/sj.jid.5701205. Epub 2008 Jan 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cohort Studies
  • DNA Mutational Analysis
  • Dermatitis, Atopic / ethnology
  • Dermatitis, Atopic / genetics*
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genotype
  • Heterozygote
  • Humans
  • Ichthyosis Vulgaris / ethnology
  • Ichthyosis Vulgaris / genetics*
  • Intermediate Filament Proteins / genetics*
  • Japan
  • Mutation*
  • Odds Ratio
  • Phenotype


  • Intermediate Filament Proteins
  • filaggrin