Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Nat Genet. 2006 Apr;38(4):441-6. doi: 10.1038/ng1767. Epub 2006 Mar 19.

Abstract

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asthma / genetics
  • Asthma / immunology
  • Child
  • Cohort Studies
  • Dermatitis, Atopic / genetics*
  • Dermatitis, Atopic / immunology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / immunology
  • Intermediate Filament Proteins / physiology*
  • Male
  • Mutation*
  • Pedigree
  • Skin Physiological Phenomena*

Substances

  • Intermediate Filament Proteins
  • filaggrin