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
Population Pharmacogenetics Group, Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Nat Genet. 2006 Apr;38(4):441-6. doi: 10.1038/ng1767. Epub 2006 Mar 19.
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.
特应性疾病，包括特应性皮炎（湿疹）、过敏和哮喘，在近几十年中发病率不断上升，目前影响着发达国家约20%的人口。双胞胎和家族研究表明，特应性疾病的易感性具有高度遗传性。尽管大多数基因研究都集中在免疫机制上，但人们已经预见到存在原发性上皮屏障缺陷。丝聚合蛋白是一种关键蛋白质，它促进表皮的终末分化和皮肤屏障的形成。在此我们表明，编码丝聚合蛋白（FLG）的基因中的两个独立的功能丧失型基因变异（R510X和2282del4）是特应性皮炎的非常强的易感因素。欧洲血统的人群中约9%携带这些变异。这些变异还与在特应性皮炎背景下发生的哮喘高度相关。这项研究确立了皮肤屏障功能受损在特应性疾病发生发展中的关键作用。
