The role of a genetically impaired epidermal barrier as a major predisposing factor in the pathogenesis of atopic disorders

The role of a genetically impaired epidermal barrier as a major predisposing factor in the pathogenesis of atopic disorders is currently under closer investigation. Vari­ ants on three candidate genes (SPINK5, KLK7 and FLG) have been associated with atopic dermatitis. A functional relevance has already been established for filaggrin vari­ ants, but not for SPINK5 and KLK7 polymorphisms. The objectives of this study were to confirm the association between SPINK5, KLK7, FLG variants and atopic der­ matitis and to assess how variants influence selected pheno­ typic traits. This cross­sectional study was carried out over 20 months in 99 children and adults with atopic der­ matitis (median age 7 years). The following items were an­ alysed: SCORAD, TEWL, ichthyosis vulgaris, presence of asthma, total IgE serum levels. The SPINK5 E420K SNP, the KLK7 4bp insertion polymorphism and the fil­ aggrin mutants (R510X and 2282del4) were analysed as described previously. The control group for genetic ana­ lysis was recruited in an ethnically matched, phenotypi­ cally anonymous cohort (n=102). The allelic frequencies were 0.525 for SPINK5, 0.26 for KLK7 polymorphisms, 0.101 and 0.075 for 2282del4 and R501X FLG mutants, respectively. The association of atopic dermatitis with fil­ aggrin variants was confirmed, but not that of SPINK5 or KLK7 polymorphisms. SCORAD and TEWL meas­ urements were not influenced by any of the variants. The SPINK5 polymorphism was associated with high IgE serum levels (p=0.011). Abnormal barrier genes do not influence the severity of atopic dermatitis. The SPINK5 gene polymorphism may modulate systemic immune ef­ fects favouring the IgE response to atopens. TEWL does not allow the characterization of subsets of patients with or without abnormal barrier genes.