Details

Autor(en) / Beteiligte

• McLean, W H Irwin
• 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

Titel

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

Ist Teil von

• Nature genetics, 2006-04, Vol.38 (4), p.441-446

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2006

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects ∼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 ∼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.