학술논문
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.
Document Type
Article
Author
Palmer, Colin N. A.; Irvine, Alan D.; Terron-Kwiatkowski, Ana; Yiwei Zhao; Haihui Liao; 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
Source
Subject
*ATOPIC dermatitis
*ALLERGIES
*ASTHMA
*GENETICS
*POPULATION
DEVELOPED countries
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Language
ISSN
1061-4036
Abstract
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. [ABSTRACT FROM AUTHOR]