miR-196a-2 rs11614913 polymorphism is associated with vitiligo by affecting heterodimeric molecular complexes of Tyr and Tyrp1
miR-196a-2 rs11614913 polymorphism is associated with vitiligo by affecting heterodimeric molecular complexes of Tyr and Tyrp1
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miR-196a-2 rs11614913 多态性通过影响 Tyr 和 Tyrp1 异二聚体分子复合物与白癜风相关
DOI：
10.1007/s00403-015-1563-1
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发表时间：
2015-10-01
影响因子：
3
通讯作者：
Li, K.
中科院分区：
文献类型：
--
作者：
Cui, T. -T.;Yi, X. -L.;Li, K.
酪氨酸酶和酪氨酸酶相关蛋白1（Tyr-Tyrp 1）复合物在黑色素中间体的合成中起着关键作用，参与活性氧（ROS）的产生，促进白癜风的发生发展。基于我们先前观察到miR-196 a-2中的rs 11614913单核苷酸多态性（SNP）可以通过影响Tyrp 1影响白癜风的风险，我们假设相同的SNP也可以调节Tyrin白癜风的水平。本研究旨在探讨miR-196 a-2中rs 11614913 SNP与白癜风患者血清Tyr水平的关系，以及miR-196 a-2对黑素细胞Tyrin表达的调控作用。采用ELISA平板法检测116例白癜风患者和116例健康对照者血清Tyr水平。通过蛋白质印迹分析PIG 1（正常黑素细胞系）细胞中Tyrp 1和Tyr的表达水平。流式细胞仪检测转染si-Tyror对照siRNA的PIG 1细胞的ROS水平和凋亡率。结果显示，miR-196 a-2 TT+TC基因型和血清Tyr水平高的个体与CC基因型和Tyr水平低的个体相比，患白癜风的风险增加（P< 0.001）。此外，miR-196 a-2中的rs 11614913 C等位基因增强了其对Tyr表达的抑制性调节，在黑素细胞中Tyr的下调成功地降低了细胞内ROS水平和细胞凋亡率。结论：miR-196 a-2基因多态性可调控酪氨酸水平，从而影响白癜风的易感性。
Tyrosinase and tyrosinase-related protein 1 (Tyr-Tyrp1) complex plays a critical role in the synthesis of melanin intermediates, which involves the production of reactive oxygen species (ROS) and contributes to the development of vitiligo. Based on our previous observation that rs11614913 single nucleotide polymorphism (SNP) in miR-196a-2 could affect the risk of vitiligo by influencingTyrp1, we hypothesized that the same SNP could also regulate the level ofTyrin vitiligo. The aim of this study was to evaluate the potential association between rs11614913 SNP in miR-196a-2 and serum Tyr level in vitiligo and the regulatory role of miR-196a-2 in the expression ofTyrin melanocytes. The serum Tyr level was detected in 116 patients with vitiligo and 116 controls by ELISA plate assay. The expression level of Tyrp1 and Tyr in PIG1(normal melanocyte cell lines) cells was analyzed by western blotting. The ROS level and apoptosis rate in PIG1 cells transfected with si-Tyror control siRNA were tested by flow cytometry. The results show that the individuals with TT+TC genotypes in miR-196a-2 and higher Tyr level in serum had an increased risk of vitiligo compared with those who had the CC genotype and lower Tyr level (P< 0.001). Furthermore, the rs11614913 C allele in miR-196a-2 enhanced its inhibitory regulation on the expression ofTyr,the down-regulation of which in melanocytes successfully reduced the intracellular ROS levels and the apoptosis rate. In conclusion, our findings suggest that miR-196a-2 polymorphisms can regulate the Tyr levels, which influences the susceptibility of vitiligo.