GARY S.WOODMDCRAIG A.ELMETSMDMOLLY A.HINSHAWMDJAY C.KLEMMEMD, MPHMARK R.PITTELKOWMDMARTIN A.WEINSTOCKMD, PhDDAVID T.WOODLEYMD
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.
Zirwas MJ. The Role of Filaggrin Mutations as an Etiologic Factor in Atopic Dermatitis. Arch Dermatol. 2007;143(11):1437-1438. doi:10.1001/archderm.143.11.1437