miRNA Copy Number Variants Confer Susceptibility to Acute Anterior Uveitis With or Without Ankylosing Spondylitis.
miRNA Copy Number Variants Confer Susceptibility to Acute Anterior Uveitis With or Without Ankylosing Spondylitis.
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DOI：
10.1167/iovs.16-21047
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发表时间：
2017-04
影响因子：
4.4
通讯作者：
Lu Yang;L. Du;Yingying Yue;Yike Huang;Qingyun Zhou;Shuang Cao;Jian-Yan Qi;L. Liang;Lili Wu;Chaokui Wang;Z. Ye;Yuan Tian;A. Kijlstra;Shengping Hou;Peizeng Yang
中科院分区：
文献类型：
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作者：
Lu Yang;L. Du;Yingying Yue;Yike Huang;Qingyun Zhou;Shuang Cao;Jian-Yan Qi;L. Liang;Lili Wu;Chaokui Wang;Z. Ye;Yuan Tian;A. Kijlstra;Shengping Hou;Peizeng Yang
目的探讨微小RNA(MiRNA)拷贝数变异(CNV)与伴或不伴强直性脊柱炎(AS)的急性前葡萄膜炎(AAU)的关系，并探讨其发病机制。方法研究对象为768例AAU+AS+或AAU+AS-患者和660例正常对照。用TaqMan聚合酶链式反应进行CNV基因分型。用实时荧光定量聚合酶链式反应、流式细胞仪或酶联免疫吸附试验检测miRNAs的表达、miR-9-3的转染率和细胞因子的产生。结果AAU+AS+患者的miR-143、miR-146a、miR-9-3、miR-205低拷贝数和miR-301a、miR-23a高拷贝数的频率增加(P=3.725×10-5~8.033×10-9)。此外，AAU+AS患者miR-146a低拷贝数和miR-23a、miR-205高拷贝数的频率显著增加(P=0.002~0.001)。与AAU+AS-组相比，AAU+AS+组miR-205低拷贝数频率明显增加(P=0.001)。AAU+AS+患者miR-9-3mRNA表达明显低于正常对照组，并与其拷贝数呈正相关。此外，人原代视网膜色素上皮细胞IL-1β和IL-6的产生受miR-9-3的调节。结论miR-143、miR-146a、miR-9-3、miR-205基因拷贝数低，miR-301a、miR-23a基因拷贝数高与AAU+AS+易感性有关。MiR-146a的低拷贝数、miR-23a和miR-205的高拷贝数与AAU+AS-相关。
Purpose To investigate the association of microRNA (miRNA) copy number variants (CNVs) with acute anterior uveitis (AAU) with or without ankylosing spondylitis (AS) and to assess underlying disease mechanisms. Methods This study included 768 patients with AAU+AS+ or AAU+AS- and 660 controls from a Chinese Han population. Genotyping of CNVs was performed by TaqMan PCR. The expression of miRNAs, transfection efficiency of miR-9-3, and cytokine production were measured by real-time PCR, flow cytometry, or ELISA. Results The frequency of low copy numbers of miR-143, miR-146a, miR-9-3, and miR-205 and of high copy numbers of miR-301a and miR-23a was increased in patients with AAU+AS+ (P = 3.725 × 10-5 to 8.033 × 10-9). Additionally, the frequency of a low copy number of miR-146a and a high copy number of miR-23a and miR-205 was significantly increased in AAU+AS- patients (P = 0.002-0.001). The frequency of low copy number of miR-205 was increased in AAU+AS+ compared with AAU+AS- (P = 0.001). The mRNA expression of miR-9-3 was significantly decreased in patients with AAU+AS+ compared with controls and positively associated with its copy number. Additionally, the production of IL-1β and IL-6 was shown to be regulated by miR-9-3 in human primary retinal pigment epithelial cells. Conclusions Low gene copy numbers of miR-143, miR-146a, miR-9-3, miR-205 and high gene copy numbers of miR-301a and miR-23a were associated with susceptibility to AAU+AS+. A low copy number of miR-146a and a high copy number of miR-23a and miR-205 were associated with AAU+AS-.