title: Filaggrin gene defects and the risk of developing allergic disorders.
abstract: Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and have been shown to be major predisposing factors for atopic dermatitis (AD). Approximately 40 loss-of-function FLG mutations have been identified in patients with ichthyosis vulgaris (IV) and/or atopic dermatitis (AD) in Europe and Asia. Major differences exist in the spectra of FLG mutations observed between different ancestral groups. Notably, prevalent FLG mutations are distinct between European and Asian populations. Many cohort studies on FLG mutations in AD have revealed that approximately 25-50% of AD patients harbour filaggrin mutations as a predisposing factor. In addition, FLG mutations are significantly associated with AD-associated asthma. The risk for developing allergic rhinitis is also significantly higher with a FLG mutation, both with and without accompanying AD. Recent studies have hypothesized that skin barrier defects caused by FLG mutations allows allergens to penetrate the epidermis and to interact with antigen-presenting cells, leading to the development of atopic disorders including asthma. The restoration of skin barrier function seems a feasible and promising strategy for prophylactic treatment of AD patients with FLG mutations.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Japan. r-osawa@fm2.seikyou.ne.jp
authors.forename: Rinko
authors.initials: R
authors.lastname: Osawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D016112:Ichthyosis Vulgaris / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D012867:Skin / Q000276:immunology
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins