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- Title
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.
- Authors
Palmer, Colin N A; Irvine, Alan D; Terron-Kwiatkowski, Ana; Zhao, Yiwei; Liao, Haihui; Lee, Simon P; Goudie, David R; Sandilands, Aileen; Campbell, Linda E; Smith, Frances J D; O'Regan, Gráinne M; Watson, Rosemarie M; Cecil, Jo E; Bale, Sherri J; Compton, John G; DiGiovanna, John J; Fleckman, Philip; Lewis-Jones, Sue; Arseculeratne, Gehan; Sergeant, Ann; Munro, Colin S; El Houate, Brahim; McElreavey, Ken; Halkjaer, Liselotte B; Bisgaard, Hans; Mukhopadhyay, Somnath; McLean, W H Irwin
- 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
Nature genetics, 2006, Vol 38, Issue 4, p441
- ISSN
1061-4036
- Publication type
Journal Article
- DOI
10.1038/ng1767