Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis by 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 GrĂ¡inne 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 in Nature genetics (2006).

[PMID: 16550169] PubMed


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.

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