Loss-of-function mutations within the filaggrin gene and atopic dermatitis

Research output: Chapter in Book/Report/Conference proceedingChapter

17 Citations (Scopus)

Abstract

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disorder that is frequently associated with elevated serum IgE levels and a personal or family history of AD, allergic rhinitis and/or asthma. Filaggrin is a major constituent of the stratum corneum (SC) and contributes to keratin filament aggregation. Its breakdown products form natural moisturizing factor, which plays a central role in hydration of the SC. Sequence analysis and epidemiological studies indicate that loss-of-function mutations in the filaggrin gene known to cause the autosomal dominant scaly skin disorder ichthyosis vulgaris are major genetic predisposing factors of AD. Mutations in filaggrin are also associated with atopic asthma. These findings established the 'filaggrin hypothesis,' which states that AD can be triggered by the chronic exposure of barrier-disrupted skin to percutaneous antigens due to abnormalities in filaggrin. In this chapter, we summarize the genome-wide screening of AD susceptibility loci, filaggrin biochemistry and recent epidemiological studies on filaggrin mutations and allergic diseases. We also summarize recent advances in the study of skin barrier mechanisms and filaggrin-associated skin barrier abnormalities in animal models. Taken together, these findings provide novel perspectives on the pathophysiology of AD and effective therapeutic methods for the treatment and/or prevention of AD through the modification of skin barrier dysfunction.

Original languageEnglish
Title of host publicationPathogenesis and Management of Atopic Dermatitis
PublisherS. Karger AG
Pages35-46
Number of pages12
Volume41
ISBN (Print)9783805596879, 9783805596862
DOIs
Publication statusPublished - 2011 May 9

Fingerprint

Atopic Dermatitis
Mutation
Genes
Skin
Cornea
Eczematous Skin Diseases
Epidemiologic Studies
Ichthyosis Vulgaris
Asthma
Skin Abnormalities
filaggrin
Keratins
Causality
Biochemistry
Immunoglobulin E
Sequence Analysis
Animal Models
Genome
Antigens
Serum

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Kawasaki, H., Kubo, A., Sasaki, T., & Amagai, M. (2011). Loss-of-function mutations within the filaggrin gene and atopic dermatitis. In Pathogenesis and Management of Atopic Dermatitis (Vol. 41, pp. 35-46). S. Karger AG. https://doi.org/10.1159/000323291

Loss-of-function mutations within the filaggrin gene and atopic dermatitis. / Kawasaki, Hiroshi; Kubo, Akiharu; Sasaki, Takashi; Amagai, Masayuki.

Pathogenesis and Management of Atopic Dermatitis. Vol. 41 S. Karger AG, 2011. p. 35-46.

Research output: Chapter in Book/Report/Conference proceedingChapter

Kawasaki, H, Kubo, A, Sasaki, T & Amagai, M 2011, Loss-of-function mutations within the filaggrin gene and atopic dermatitis. in Pathogenesis and Management of Atopic Dermatitis. vol. 41, S. Karger AG, pp. 35-46. https://doi.org/10.1159/000323291
Kawasaki H, Kubo A, Sasaki T, Amagai M. Loss-of-function mutations within the filaggrin gene and atopic dermatitis. In Pathogenesis and Management of Atopic Dermatitis. Vol. 41. S. Karger AG. 2011. p. 35-46 https://doi.org/10.1159/000323291
Kawasaki, Hiroshi ; Kubo, Akiharu ; Sasaki, Takashi ; Amagai, Masayuki. / Loss-of-function mutations within the filaggrin gene and atopic dermatitis. Pathogenesis and Management of Atopic Dermatitis. Vol. 41 S. Karger AG, 2011. pp. 35-46
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