Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular - Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Gene. 2019 Jun 5;700:17-22. doi: 10.1016/j.gene.2019.03.026. Epub 2019 Mar 16.
The weaker expression of the two main proteins adhering melanocytes to the epidermis basal layer, Epithelial Cadherin (E-cadherin) and Discoidin Domain Receptor Tyrosine kinase 1 (DDR1), has been implicated as one of the aggravating factors in the loss of melanocytes in vitiligo. The present study was designed to assess the association between single nucleotide polymorphisms (SNP) in the genes encoding these proteins, CDH1 and DDR1, and the risk of developing vitiligo. The independent case-control study was conducted on the sample including152 patients with vitiligo and 152 matched controls. A questionnaire was completed for recording demographic and clinical characteristics of vitiligo patients. Venous blood samples were taken from all the subjects. Genotype frequencies were determined for CDHI C/T (rs 10431924) and DDRI A/C (rs 2267641) genes polymorphisms using polymerase chain reaction (PCR) amplification method and Restriction Fragment Length Polymorphism (RFLP) analysis. The CDH1 CC genotype was found to be significantly associated with the risk of developing vitiligo. The results of stratified analysis revealed a correlation between CDH1 CC genotype and late age of onset, clinical type of vitiligo, the absence of autoimmune comorbidities and family history of autoimmune disorders. However, the expression level of CDH1 TT genotype increased significantly in patients with autoimmune comorbidities. There was also a significant relationship between the DDR1 CC genotype and the risk of developing vitiligo. The results of stratified analysis revealed a correlation between DDR1 CC genotype and early age of onset, clinical type of vitiligo and absence of family history of autoimmune disorders. The findings of the study confirm the conjecture previously made in the literature regarding the melanocytes' adhesion deficit as an initial step for pigment loss in vitiligo and emphasize the substantial role of friction and koebner phenomenon in the pathogenesis of vitiligo. Moreover, a probable association can be proposed between the adhesion deficit involved in vitiligo and autoimmune disorders.
两种主要的蛋白质（上皮钙黏蛋白[E-cadherin]和盘状结构域受体酪氨酸激酶 1[DDR1]）表达减弱，被认为是白癜风中黑素细胞丧失的加重因素之一。本研究旨在评估编码这些蛋白（CDH1 和 DDR1）的基因中单核苷酸多态性（SNP）与发生白癜风风险之间的关系。这项独立的病例对照研究在包括 152 例白癜风患者和 152 例匹配对照的样本中进行。通过问卷调查记录白癜风患者的人口统计学和临床特征。从所有受试者中抽取静脉血样本。采用聚合酶链反应（PCR）扩增法和限制性片段长度多态性（RFLP）分析检测 CDH1 C/T（rs10431924）和 DDR1 A/C（rs2267641）基因多态性的基因型频率。发现 CDH1 CC 基因型与发生白癜风的风险显著相关。分层分析结果显示，CDH1 CC 基因型与发病年龄晚、白癜风临床类型、无自身免疫合并症和自身免疫性疾病家族史相关。然而，CDH1 TT 基因型的表达水平在伴自身免疫合并症的患者中显著增加。DDR1 CC 基因型与发生白癜风的风险也存在显著关系。分层分析结果显示，DDR1 CC 基因型与发病年龄早、白癜风临床类型和无自身免疫性疾病家族史相关。该研究的结果证实了文献中先前提出的关于黑素细胞黏附缺陷作为白癜风色素丧失初始步骤的假说，并强调了摩擦和 Koebner 现象在白癜风发病机制中的重要作用。此外，还可以提出与白癜风和自身免疫性疾病相关的黏附缺陷之间的可能关联。
