Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
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DOI：
10.1038/ng1767
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发表时间：
2006-04-01
期刊：
影响因子：
30.8
通讯作者：
McLean, WHI
中科院分区：
文献类型：
--
作者：
Palmer, CNA;Irvine, AD;McLean, WHI
特应性疾病，包括特应性皮炎（湿疹），过敏和哮喘，在最近几十年中频率增加（1），现在影响发达国家约20%的人口。双胞胎和家庭研究表明，特应性疾病的易感性是高度遗传的（2）。虽然大多数遗传学研究都集中在免疫学机制上，但预期会出现原发性上皮屏障缺陷（3）。聚丝蛋白是促进表皮终末分化和皮肤屏障形成的关键蛋白。在这里，我们表明，两个独立的功能丧失的基因变异（R510X和2282del4）的基因编码聚丝蛋白（FLG）是非常强的诱发因素特应性皮炎。这些变异携带了近似9%的欧洲血统的人。这些变异体还显示出与特应性皮炎背景下发生的哮喘高度显著相关。这项工作确立了皮肤屏障功能受损在特应性疾病发展中的关键作用。
Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades(1) and now affects similar to 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable(2). Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated(3). 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 similar to 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.