title: Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan.
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.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Nomura
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Aileen
authors.initials: A
authors.lastname: Sandilands
authors.forename: Ikue
authors.initials: I
authors.lastname: Nemoto-Hasebe
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakai
authors.forename: Akari
authors.initials: A
authors.lastname: Nagasaki
authors.forename: Mitsuhito
authors.initials: M
authors.lastname: Ota
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hata
authors.forename: Alan T
authors.initials: AT
authors.lastname: Evans
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003876:Dermatitis, Atopic / Q000208:ethnology / Q000235:genetics*; D000091344:Filaggrin Proteins; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000208:ethnology / Q000235:genetics*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D007564:Japan; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins