Hisako Enomoto

Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population: a family and case–control study

AbstractFilaggrin (FLG) plays an important role in the barrier function of the skin. Several loss-of-function mutations in the FLG gene have been identified in patients with ichthyosis vulgaris, and these null mutations are associated with atopic dermatitis (AD) development. In this study, we examined tag single nucleotide polymorphisms (tSNPs) and null mutations in FLG for possible associations with AD and atopic phenotypes in a Japanese population. Transmission disequilibrium test of 105 AD families showed that the null allele of the S2554X variant of FLG tended to be overtransmitted to AD-affected offspring; however, the P value did not reach statistical significance. In a case–control comparison of 376 AD cases and 923 nonallergic controls, the null allele of S2554X was significantly associated with AD (P = 0.0012), and the association was strengthened in subjects with AD alone (P = 0.000024). We found that 3321delA and S2554X were also associated with elevated levels of immunoglobulin E (IgE). Combined null mutation carriers were observed more in AD patients and in subjects with high IgE than in control subjects. The combined P value for the family and case–control data was significant for the S2554X and combined null mutations. Our data further support the importance of FLG in AD development.

Single nucleotide polymorphism-based genome-wide linkage analysis in Japanese atopic dermatitis families

BackgroundAtopic dermatitis develops as a result of complex interactions between several genetic and environmental factors. To date, 4 genome-wide linkage studies of atopic dermatitis have been performed in Caucasian populations, however, similar studies have not been done in Asian populations. The aim of this study was to identify chromosome regions linked to atopic dermatitis in a Japanese population.MethodsWe used a high-density, single nucleotide polymorphism genotyping assay, the Illumina BeadArray Linkage Mapping Panel (version 4) comprising 5,861 single nucleotide polymorphisms, to perform a genome-wide linkage analysis of 77 Japanese families with 111 affected sib-pairs with atopic dermatitis.ResultsWe found suggestive evidence for linkage with 15q21 (LOD = 2.01, NPL = 2.87, P = .0012) and weak linkage to 1q24 (LOD = 1.26, NPL = 2.44, P = .008).ConclusionWe report the first genome-wide linkage study of atopic dermatitis in an Asian population, and novel loci on chromosomes 15q21 and 1q24 linked to atopic dermatitis. Identification of novel causative genes for atopic dermatitis will advance our understanding of the pathogenesis of atopic dermatitis.

A rare variant in CYP27A1 and its association with atopic dermatitis with high serum total IgE

This study investigated rare variants associated with atopic dermatitis. We performed exome analyses on 37 patients who were diagnosed with atopic dermatitis by board‐certified dermatologists and had total serum IgE levels greater than 1000 IU/ml. The exome analysis identified seven variants with <1% allele frequency in Asian (ASN) population of 1000 Genomes Project phase 1 data and >5% allele frequency in the atopic dermatitis exome samples. We then conducted a replication study using 469 atopic dermatitis patients with total serum IgE ≥1000 IU/ml and 935 Japanese controls to assess the presence of these 7 candidate variants. The replication study confirmed that CYP27A1 rs199691576 (A/G) was associated with atopic dermatitis with high serum IgE levels (P = 0.012, odds ratio = 2.1). CYP27A1 is involved in the metabolism of vitamin D3, which plays important roles in modulating immune function. Previous studies have reported polymorphisms in vitamin D pathway genes that are associated with allergy‐related phenotypes. Our data confirm the importance of genes regulating the vitamin D pathway in the development of atopic dermatitis.

A case of syringoid eccrine carcinoma with circumscribed abundant stroma

Editor Syringoid eccrine carcinoma is a rare tumour that shows a slow growth and has often been present for many years, sometimes decades, before diagnosis. 1 Histologically, the tumour is characterized by syringoma-like tadpole morphology composed of basaloid cells with ductular differentiation. However, the tumour cells are deeply invasive and often extend to subcutaneous tissue, which distinguishes this malignancy from syringoma. Another feature is that the tumour sets in a dense fibrous stroma, although the mechanism underlying this feature has not been clarified. 1 We here report a case of syringoid eccrine carcinoma forming circumscribed tumour nests with abundant stroma. A 64-year-old woman presented with 3 months history of a 10-mm diameter, painful, firm plaque on the right forehead. The lesion surgically removed showed multiple tumour nodules proliferating in dermis and subcutaneous adipose tissue (Fig. 1a). Each nodule includes abundant stromal tissue (Fig. 1b). The tumour consisted of basaloid cells arranging in narrow cords and partially forming ductular structure. Tadpole-like forms were sometimes observed. Mitoses were also found (Fig. 1c) but not prominent. Squamous or follicular differentiation was not seen. Immunohistochemical staining of tumour cells showed positive reactivity to epithelial membrane antigen and carcinoembryonic antigen (Fig. 1d) but negative reactivity to S-100 protein. The stroma positively stained for type 1 collagen but not type 2, type 3 and type 4 collagens, fibronectin, laminin and vimentin. In addition, the immunostaining of tumour cells did not detect expression of type 1 collagen and fibrosis-associated cytokines including fibroblast growth factor 1 and 2, transforming growth factor-beta, platelet-derived growth factor, hepatocyte growth factor/scatter factor and insulin-like growth factor 1. This case required differential diagnosis with microcystic adnexal carcinoma, which is also surrounded by a dense fibrous stroma and infiltrates into the deeper tissue. 1 Absence of keratinfilled cyst and follicular differentiation resulted in the diagnosis of syringoid eccrine carcinoma; nevertheless, the assessment was difficult. In both syringoid eccrine carcinoma and microcystic adnexal carcinoma, the surrounding stroma is generally ill defined because tumour nests proliferate chiefly in dermis. It has therefore been unknown whether the stroma surrounding tumour nests is induced by a direct effect of tumour-derived cytokine or non-specific

Prevalence of atopic dermatitis in Japanese infants treated with moisturizer since birth and its relation to FLG mutations

ejd.2013.1960 Auteur(s) : Yusuke Inoue1,a yuh-yuh15@hotmail.co.jp, Ryoko Nakagawara1,a, Takeshi Kambara2, Kimiyo Tanaka1, Kazuo Seki3, Hisako Enomoto4, Emiko Noguchi4, Michiko Aihara1, Zenro Ikezawa1 1 Department of Environmental Immuno-Dermatology, 2 Department of Dermatology, 3 Department of Perinatal Center, Yokohama City University Medical Center, Yokohama, Japan 4 Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan a Y. Inoue [...]

SMAD3 as an atopic dermatitis susceptibility gene in the Japanese population

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Interleukin-8 and CXCR2 expression in spindle cell haemangioendothelioma.

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A case of proximal-type epithelioid sarcoma which showed positive reactivity to fibroblast growth factor receptor2-IIIb isotype

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