中华皮肤科杂志 ›› 2014, Vol. 47 ›› Issue (4): 251-254.

• 论著 • 上一篇    下一篇

寻常型鱼鳞病患者皮损中间丝聚合蛋白及其基因的改变

李常兴1,李雪梅2,张锡宝3,韩春雷4,马泽粦5   

  1. 1. 南方医科大学南方医院
    2.
    3. 广州市皮肤病防治所
    4. 广东东莞慢性病防治所
    5. 东莞市慢性病防治院
  • 收稿日期:2013-06-26 修回日期:2013-10-02 出版日期:2014-04-15 发布日期:2014-04-01
  • 通讯作者: 张锡宝 E-mail:zxibao@126.com
  • 基金资助:
    广东省东莞市医疗卫生单位科技计划项目;国家自然科学基金;广东省东莞市医疗卫生单位科技计划项目

Changes of filaggrin and its gene in patients with ichthyosis vulgaris

  • Received:2013-06-26 Revised:2013-10-02 Online:2014-04-15 Published:2014-04-01
  • Supported by:
    ; National Natural Science Foundation of China

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摘要： 【摘要】 目的 探讨寻常型鱼鳞病患者中间丝聚合蛋白（FLG）基因突变与FLG及兜甲蛋白在寻常型鱼鳞病患者皮损组织中的表达及其临床意义。 方法 采用SP免疫组化方法检测10例汉族寻常型鱼鳞病患者皮损及14例健康对照皮肤组织内FLG及兜甲蛋白的表达，用图像分析软件ImagePro plus（IPP）判定FLG及兜甲蛋白在寻常型鱼鳞病患者皮损及正常皮肤组织中表达的阳性单位（PU值）。提取10例汉族寻常型鱼鳞病患者及100例健康对照者的基因组DNA，采用PCR及直接测序法，对FLG基因已报道的13个突变位点（3321delA、441delA、1249insG、E1795X、S3296X、R501X、2282del4、R2447X、S2889X、7945delA、3702delG、Q2417X、R4307X）进行测序。 结果 FLG在寻常型鱼鳞病皮损及健康对照皮肤角质层、颗粒层、棘层及基底层细胞均有表达，胞质染色多见；寻常型鱼鳞病皮损阳性染色PU值明显低于健康对照皮肤（分别为0.2082 ± 0.0080和0.2300 ± 0.0228，两组比较，t = 3.30，P < 0.01）。兜甲蛋白在寻常型鱼鳞病皮损及健康对照皮肤颗粒层、棘层及基底层细胞均有表达，胞质及胞核染色多见；寻常型鱼鳞病皮损表达的PU值明显低于健康对照皮肤（分别为0.1370 ± 0.0112和0.1493 ± 0.0073，两组比较，t = 3.07，P < 0.01）。7例寻常型鱼鳞病患者检测到FLG 3321delA突变位点，2例检测到FLG 441delA突变位点，健康对照组未检测到FLG基因突变位点。 结论 FLG（3321delA，441delA）可能是汉族寻常型鱼鳞病患者的突变位点之一。FLG及兜甲蛋白表达下降可能与寻常型鱼鳞病患者皮肤屏障功能障碍有关。

关键词: 鳞癣，寻常, 突变, 中间丝聚合蛋白, 兜甲蛋白

Abstract: Li Changxing*, Li Xuemei, Zhang Xibao, Han Chunlei, Ma Zelin. *Department of Dermatology, Dongguan Municipal Hospital for Chronic Disease Prevention and Control, Dongguan 523008, Guangdong, China Corresponding author: Zhang Xibao, Email: zxibao@126.com 【Abstract】 Objective To detect mutations in the filaggrin （FLG） gene and expressions of FLG and loricrin in patients with ichthyosis vulgaris （IV）, and to investigate their clinical significance. Methods Tissue specimens were resected from the skin lesions of 10 patients with IV and normal skin of 14 healthy human controls, and immunohistochemical SP method was used to detect the expressions of filaggrin and loricrin. The expression intensity was determined by the Image-Pro Plus （IPP） software, and expressed as positive units （PU）. Blood samples were collected from 10 patients of Han nationality with IV and 100 healthy human controls followed by DNA extraction. PCR and DNA sequencing were performed to detect the presence of 13 mutations （3321delA, 441delA, 1249insG, E1795X, S3296X, R501X, 2282del4, R2447X, S2889X, 7945delA, 3702delG, Q2417X, R4307X） in the FLG gene. Results FLG was mainly expressed in the cytoplasm of keratinocytes in the stratum corneum, granular layer, prickle layer and basal layer, and loricrin was observed in the cytoplasm and nuclei of keratinocytes in the granular layer, prickle layer and basal layer, in both the lesional and normal skin. Compared with the normal skin, the lesional skin showed significantly weaker expressions of FLG （0.208 2 ± 0.008 0 vs. 0.230 0 ± 0.0228, t = 3.30, P < 0.01） and loricrin （0.137 0 ± 0.011 2 vs. 0.149 3 ± 0.007 3, t = 3.07, P < 0.01）. Sequencing analysis identified two mutations, including 3321delA in 7 patients and 441delA in 2 patients. No mutations were detected in the healthy controls. Conclusions The 3321delA and 441delA mutations in the FLG gene may represent the most frequent genetic cause of IV in patients of Han nationality. The low expressions of FLG and loricrin may be associated with the impairment of skin barrier function in patients with IV.

Key words: Ichthyosis vulgaris, Mutation, Filaggrin, Loricrin