SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis
- SourceAvailable from: Akiharu Kubo
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- "Loss-of-function mutations in SPINK5 (Chr 5q32) leading to accelerated desquamation, is the defect in Netherton's syndrome, a severe autosomal recessive ichthyotic condition characterized by a chronic atopic dermatitis-like condition, allergen sensitization and other atopic disorders such as asthma and allergic rhinitis (Frenk and Mevorah, 1972). Interestingly, coding polymorphisms in the SPINK5 gene have been found in association with AD and disease severity (Cork et al., 2009; Walley et al., 2001), and more recently with food allergy in children with AD (Kusunoki et al., 2005). Although Hubiche et al. (Hubiche et al., 2007) did not find an association in a French AD population, they did observe an association between the E420K polymorphism and serum IgE levels, suggesting that this barrier defect predisposes subjects to a Th2 response to environmental allergens. "
ABSTRACT: For at least half a century, noninvasive techniques have been available to quantify skin barrier function, and these have shown that a number of human skin conditions and disorders are associated with defects in skin permeability. In the past decade, several genes responsible for skin barrier defects observed in both monogenetic and complex polygenic disorders have been elucidated and functionally characterized. This has led to an explosion of work in the past 6 years that has identified pathways connecting epidermal barrier disruption and antigen uptake, as well as the quality and/or magnitude of the antigen-specific adaptive immune response. This review will introduce the notion that diseases arise from the dynamic crosstalk that occurs between skin barrier and the immune system using atopic dermatitis or eczema as the disease prototype. Nevertheless, the concepts put forth are highly relevant to a number of antigen-driven disorders for which skin barrier is at least transiently compromised, such as psoriasis, allergic contact dermatitis, and blistering disorders.Journal of Investigative Dermatology 01/2012; 132(3 Pt 2):949-63. DOI:10.1038/jid.2011.435 · 6.37 Impact Factor
- "122, 689–93s.) and infection via the skin (Chavanas et al., 2000; Walley et al., 2001). A E420K single nucleotide polymorphism (SNP) variant in the SPINK5 gene has shown significant association with disease severity and with the presence of food allergy in children with AD (Kusunoki et al., 2005). Other protease inhibitors with similar roles to SPINK5 are encoded by a cluster of genes on chromosome 20q12, close to a region that has been linked to AD. "
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- "Mutations in SPINK5 cause Netherton syndrome in which atopy is a universal accompaniment. Variants in SPINK5 provide susceptibility to AD (Walley et al., 2001; Kato et al., 2003; Nishio et al., 2003; Kusunoki et al., 2005), though no association was seen in one study (Folster-Holst et al., 2005). These associations with SPINK5 mutations and variants support the hypothesis that a dysfunctional skin barrier predisposes to AD (Cookson, 2004). "
ABSTRACT: Atopic dermatitis (AD) results from strong genetic and environmental interactions. AD shows genetic linkage to Chromosome 1q21. This region contains the epidermal differentiation complex (EDC), which consists of genes that form essential components of epidermal surfaces. Filaggrin (FLG) is one of these. Mutations in FLG/(R501X and 2282del4) are reported to be strongly associated with AD and to influence asthma accompanying AD. We investigated these effects in families recruited through a child with severe AD. We genotyped two panels of families, totalling 426, containing 990 affected and unaffected children. We found significant associations with AD (P=0.0001), asthma (P=0.006), and atopy (P=0.002). The FLG mutations were present in 26.7% of patients with AD, but were also present in 14.4% of children without AD. They were weakly associated with disease severity. The variants were not independently associated with asthma. The overall LOD score for genetic linkage of markers to the region was 3.57. This fell to 2.03 after accounting for the FLG mutations, indicating the presence of other genetic variants influencing AD at this locus. Our results provide further confirmation of the importance of mutations in FLG and the skin barrier in AD pathogenesis. The results indicate that investigations of other genes within the EDC should be undertaken.Journal of Investigative Dermatology 08/2007; 127(7):1667-72. DOI:10.1038/sj.jid.5700739 · 6.37 Impact Factor