Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, , Chongqing, P R China.
Ann Rheum Dis. 2014 Jan;73(1):170-6. doi: 10.1136/annrheumdis-2012-201627. Epub 2012 Dec 25.
MicroRNA-146a (miR-146a) is involved in certain immune-mediated diseases. Transcription factor Ets-1 strongly affects miR-146a promoter activity and directly regulates miR-146a expression. This study was performed to investigate the association of miR-146a and Ets-1 gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) disease in a Chinese Han population.
A total of 809 patients with BD, 613 patients with VKH and 1132 normal controls were genotyped for miR-146a/rs2910164, rs57095329 and rs6864584, Ets-1/rs1128334 and rs10893872 using a PCR restriction fragment length polymorphism assay. miR-146a expression was examined in peripheral blood mononuclear cells (PBMCs) by real-time PCR. Cytokine production by PBMCs was measured by ELISA.
A significantly decreased frequency of the homozygous rs2910164 CC genotype and C allele was observed in patients with BD compared with controls (pc(a)=1.24×10(-5), OR 0.61; pc(a)=1.33×10(-4), OR 0.75, respectively). MiR-146a expression in GG cases was 2.45-fold and 1.99-fold higher, respectively, than that in CC cases and GC cases. There was no association of the other four single nucleotide polymorphisms (SNPs) with BD. There was also no association of these five SNPs with its main clinical features. No associations were found with the five SNPs tested or with its clinical manifestations in VKH disease. Interleukin (IL)-17, tumour necrosis factor (TNF)α and IL-1β production from rs2910164 CC cases was markedly lower than that in GG cases. No effect of genotype was observed on IL-6 and monocyte chemoattractant protein (MCP)-1 production and IL-8 expression was slightly higher in CC cases.
Our study identified a strong association of rs2910164 of miR-146a with BD in a Chinese population and decreased expression of miR-146a and certain proinflammatory cytokines in individuals carrying the CC genotype.
微小 RNA-146a（miR-146a）参与某些免疫介导的疾病。转录因子 Ets-1 强烈影响 miR-146a 启动子活性，并直接调节 miR-146a 的表达。本研究旨在探讨 miR-146a 和 Ets-1 基因多态性与中国汉族人群中贝切特病（BD）和 Vogt-Koyanagi-Harada（VKH）病的关系。
采用聚合酶链反应限制性片段长度多态性分析方法，对 809 例 BD 患者、613 例 VKH 患者和 1132 例正常对照者进行 miR-146a/rs2910164、rs57095329 和 rs6864584、Ets-1/rs1128334 和 rs10893872 基因多态性检测。采用实时 PCR 检测外周血单个核细胞（PBMCs）中 miR-146a 的表达。采用 ELISA 法检测 PBMCs 细胞因子的产生。
与对照组相比，BD 患者 rs2910164 纯合 CC 基因型和 C 等位基因的频率明显降低（pc(a)=1.24×10(-5)，OR 0.61；pc(a)=1.33×10(-4)，OR 0.75）。GG 病例的 miR-146a 表达分别是 CC 病例和 GC 病例的 2.45 倍和 1.99 倍。其余 4 个单核苷酸多态性（SNP）与 BD 无相关性。这五个 SNP 与 BD 的主要临床特征也没有关联。在 VKH 病中，也未发现这五个 SNP 与其临床表现相关。
本研究在中国人群中发现 miR-146a 的 rs2910164 与 BD 有很强的关联性，携带 CC 基因型的个体 miR-146a 表达降低，某些促炎细胞因子的产生减少。
