Artikel
Filaggrin mutations are strong risk factors for atopic dermatitis
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Veröffentlicht: | 6. September 2007 |
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Gliederung
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Atopic dermatitis (AD) arises from the interplay between strong genetic and environmental factors. One of its characteristic features is an impaired epidermal barrier function. A region on chromosome 1q21 which contains the epidermal differentiation complex (EDC) has been linked to AD. Recently, two loss-of-function mutations (R501X and 2282del4) within the EDC gene filaggrin (FLG) have been reported to be strongly associated with AD. In a subsequent family-based study we could show that these mutations particularly predispose to the extrinsic subtype of AD. In the present study we genotyped an independent collection of 274 adult AD cases and 252 population-based controls. Using logistic and linear regression models we found highly significant associations with AD (OR 3.53, p=4.9 x 10-5), especially extrinsic (OR 4.19, p=1.1 x 10-5) and early-onset AD (OR 5.21, p=2.8 x 10-6), as well as with elevated total IgE, asthma and rhinitis. In addition, the 2282del4 mutation was associated with a more severe phenotype (OR 3.16, 95% CI 1.49-6.72, p=0.0027). Thus, we confirm and expand previous observations that FLG mutations are strong risk factors for AD, especially extrinsic AD. The present results indicate that these mutations are also associated with an early onset and persistent course of the disease and provide further evidence for the hypothesis that a genetically-determined primary epidermal barrier disruption is the key-event in AD.