Hou Shengping, Ye Zi, Liao Dan, Bai Lin, Liu Yunjia, Zhang Jun, Kijlstra Aize, Yang Peizeng
The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
Sci Rep. 2016 Jan 28;6:20057. doi: 10.1038/srep20057.
Ninety-eight miRNAs are involved in the immune response. However, the genetic roles of these miRNAs remain unclear in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome. This study aimed to explore the association and functional roles of copy number variants (CNV) in several miRNAs with BD and VKH syndrome. Genotyping of CNVs was examined by TaqMan PCR. The expression of miR-23a, transfection efficiency and cytokine production were measured by real-time PCR, flow cytometry or ELISA. First, replication and combined studies for miR-23a, miR-146a and miR-301a demonstrated a similar association with VKH syndrome (Combined: P = 5.53 × 10(-8); P = 8.43 × 10(-31); P = 9.23 × 10(-8), respectively). No association of CNVs of the above mentioned miRNAs was observed in BD patients. mRNA expression of miR-23a showed a positive association with its copy numbers. Additionally, individuals with high copy number of miR-23a show an increased production of interleukin-6 (IL-6), but not IL-8 and monocyte chemoattractant protein-1 (MCP-1) by stimulated PBMCs. miR-23a transfected ARPE-19 cells modulated the production of IL-6 and IL-8, but not MCP-1. Our results suggest that CNVs of miR-146a, miR-23a and miR-301a confer susceptibility to VKH syndrome, but not to BD. The contribution of miR-23a to VKH syndrome may be mediated by increasing the production of IL-6.
98种微小RNA参与免疫反应。然而，这些微小RNA在白塞病（BD）和葡萄膜炎-小柳原田综合征（VKH）中的遗传作用仍不清楚。本研究旨在探讨几种微小RNA的拷贝数变异（CNV）与BD和VKH综合征的关联及功能作用。通过TaqMan PCR检测CNV的基因分型。通过实时PCR、流式细胞术或酶联免疫吸附测定法测量miR-23a的表达、转染效率和细胞因子产生。首先，对miR-23a、miR-146a和miR-301a的重复和联合研究表明，它们与VKH综合征存在相似的关联（联合分析：P分别为5.53×10⁻⁸；P为8.43×10⁻³¹；P为9.23×10⁻⁸）。在BD患者中未观察到上述微小RNA的CNV与疾病有关联。miR-23a的mRNA表达与其拷贝数呈正相关。此外，miR-23a拷贝数高的个体，其外周血单个核细胞（PBMC）经刺激后白细胞介素-6（IL-6）的产生增加，但IL-8和单核细胞趋化蛋白-1（MCP-1）的产生未增加。转染miR-23a的ARPE-19细胞可调节IL-6和IL-8的产生，但不调节MCP-1的产生。我们的结果表明，miR-146a、miR-23a和miR-301a的CNV赋予个体患VKH综合征的易感性，但与BD无关。miR-23a对VKH综合征的作用可能是通过增加IL-6的产生来介导的。
