1. ¹Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
2. ²Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
3. ³Department of Dermatology, Oji General Hospital, Tomakomai, Japan
4. ⁴Department of Pathology, Tayside University Hospitals National Health Service Trust, Dundee, UK
5. ⁵Population Pharmacogenetics Group, Biomedical Research Center, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK

Correspondence: Professor Irwin McLean, Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK. E-mail: w.h.i.mclean@dundee.ac.uk

Received 4 September 2007; Revised 12 October 2007; Accepted 15 October 2007; Published online 17 January 2008.

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 (² P=8.4 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.