Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis
Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis
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DOI：
10.1016/j.jaci.2006.12.646
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发表时间：
2007-02-01
影响因子：
14.2
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Nomura, Toshifumi;Sandilands, Aileen;Shimizu, Hiroshi
背景：聚丝蛋白是参与皮肤屏障功能的关键蛋白。目的：研究FLG基因突变在日本特应性皮炎（AD）中的作用。方法：通过基因分型研究已知的聚丝蛋白基因突变，并通过DNA测序鉴定新的突变。结果：FLG基因突变与AD的发病率呈负相关。结论：FLG基因突变与AD发病率呈负相关。253名日本人没有发现欧洲特异性突变R501X和2282del4。因此，我们对4个日本IV家族的FLG基因进行了测序，并确定了2个新的突变，3321delA和S2554X。免疫组织学和超微结构的观察表明，这两个截断突变导致显着减少角质透明质颗粒在表皮。我们筛选了143例日本AD患者的这些FLG无效突变，并在8例AD患者（5.6%）中鉴定出它们，包括6例患者（4.2%）的S2554X和2例患者（1.4%）的3321delA。在156名无关的日本非特异性和非鱼鳞病对照中，两种无效变异均不存在，这表明FLG突变与AD之间存在显著的统计学相关性（χ 2 P值，0.0015）。这是第一次报告的FLG突变在非欧洲population.Conclusion：我们的数据表明，FLG突变在日本是独特的，从那些发现在欧洲血统population.Clinical影响：丝聚蛋白无效变异也是显着的易感因素，在日本的AD，并在最近的欧洲研究的基础上，可以预测更严重和持久的形式的特应性。
Background: Filaggrin is a key protein involved in skin barrier function. Recently, mutations in the filaggrin gene, FLG, were identified in European families with ichthyosis vulgaris (IV) and shown to be an important predisposing factor for atopic dermatitis (AD).Objective: To study the role of FLG mutations in IV/AD in Japan.Methods: The known filaggrin mutations were studied by genotyping and new mutations identified by DNA sequencing.Results: The European-specific mutations R501X and 2282del4 were absent from 253 Japanese individuals. We therefore sequenced the FLG gene in 4 Japanese families with IV and identified 2 novel mutations, 3321delA and S2554X. Immunohistologic and ultrastructural observations indicated that both truncation mutations lead to a striking reduction of keratohyalin granules in the epidermis. We screened 143 Japanese patients with AD for these FLG null mutations and identified them in 8 patients with AD (5.6%), including S2554X in 6 patients (4.2%) and 3321delA in 2 patients (1.4%). Both null variants were absent from 156 unrelated Japanese nonatopic and nonichthyotic controls, giving a significant statistical association between the FLG mutations and AD (chi(2) P value, .0015). This is the first report of FLG mutations in a non-European population.Conclusion: Our data indicate that FLG mutations in Japan are unique from those found in European-origin populations.Clinical implications: Filaggrin null variants are also significant predisposing factors for AD in Japan and, on the basis of the recent European studies, may predict a more severe and persistent form of atopy.