Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population
ABSTRACT Netherton's syndrome (NS) is an autosomal recessive disorder characterized by trichorrhexis invaginata ('bamboo hair'), congenital ichthyosiform erythroderma and an atopic diathesis. NS has recently been shown to be due to a defect in the SPINK5 gene, encoding LEKTI, a 15-domain serine protease inhibitor. SPINK5 maps to chromosome 5q31-q32, and has been suggested to be a locus predisposing to atopy in general. Recently, coding polymorphisms in SPINK5 exons 13 and 14 have been reported to be associated with atopy, asthma and atopic dermatitis (AD).
To examine whether these polymorphisms are also associated with AD in Japan.
We characterized eight polymorphisms in SPINK5 exons 13 and 14 in 124 Japanese patients with AD and 110 healthy controls. The polymorphisms we examined were IVS12-26C-->T, IVS12-10A-->G, 1103A-->G (Asn368Ser, in exon 13), 1156G-->A (Asp386Asn, in exon 13), 1188T-->C (His396His, in exon 13), IVS13-50G-->A, 1258G-->A (Glu420Lys, in exon 14) and IVS14+19G-->A.
We found significant associations between seven of these polymorphisms and AD in Japanese patients.
This study confirms the previous suggestion of an association between SPINK5 and AD.
SourceAvailable from: Dug Yeo Han[Show abstract] [Hide abstract]
ABSTRACT: Background In a double-blind, randomized, placebo-controlled birth cohort, we have recently shown a beneficial effect of Lactobacillus rhamnosus HN001 (HN001) for the prevention of eczema in children through to 6 years of age but no effect of Bifidobacterium animalis subsp lactis HN019 (HN019).Objective Among this cohort of children, we aim to investigate whether these probiotics could modify the expression of genetic predisposition to eczema conferred by genetic variation in susceptibility genes.Methods Thirty three eczema susceptibility SNPs (in eleven genes) were genotyped in 331 children of European ancestry.ResultsChildren who carried a genetic variant that put them at a high risk of developing eczema were less likely to develop eczema if they had been randomised to the HN001 intervention group compared to those in the placebo group. HN019 was also able to protect against the effects of some SNPs. As well as modifying genetic susceptibility to childhood eczema, HN001 was also found to modify genetic susceptibility to eczema severity and atopy risk.Conclusion and Clinical RelevanceThis is the first study to show an effect of a probiotic on reducing eczema risk amongst those with particular eczema-associated genotypes. Our findings suggest that Lactobacillus rhamnosus HN001 may be particularly effective in preventing eczema in children with specific high risk genotypes.This article is protected by copyright. All rights reserved.Clinical & Experimental Allergy 08/2014; 44(10). DOI:10.1111/cea.12394 · 4.32 Impact Factor
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ABSTRACT: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease perpetuated by gene-environmental interactions and which is characterized by genetic barrier defects and allergic inflammation. Recent studies demonstrate an important role for the epidermal permeability barrier in AD that is closely related to chronic immune activation in the skin during systemic allergic reactions. Moreover, acquired stressors (e.g., Staphylococcus aureus infection) to the skin barrier may also initiate inflammation in AD. Many studies involving patients with AD revealed that defective skin barriers combined with abnormal immune responses might contribute to the pathophysiology of AD, supporting the outside-inside hypothesis. In this review, we discuss the recent advances in human and animal models, focusing on the defects of the epidermal permeability barrier, its immunologic role and barrier repair therapy in AD.Allergy, asthma & immunology research 07/2014; 6(4):276-87. DOI:10.4168/aair.2014.6.4.276 · 3.08 Impact Factor
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ABSTRACT: Atopic dermatitis is the result of complex interactions between environmental and genetic factors influencing the epidermal structure and function, as well as the immune system. Epidermal changes, including the defective epidermal permeability barrier, have recently been intensively investigated recently and seem to be a hallmark of disease pathogenesis. In particular, the detection of filaggrin mutations resulting in a defect in barrier formation has been a landmark finding. However, changes in the lipid metabolism and the expression of endogenous and exogenous proteases, protease inhibitors and tight junction proteins also contribute to the barrier defect in atopic dermatitis.Expert Review of Dermatology 01/2014; 7(3). DOI:10.1586/edm.12.17