The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, The People's Republic of China.
University Eye Clinic Maastricht, Maastricht, The Netherlands.
Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4820-4829. doi: 10.1167/iovs.19-27708.
This study was aimed at investigating the association of long noncoding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) with Vogt-Koyanagi-Harada (VKH) disease.
LncRNA-related SNPs were selected by multi-omics analysis. Genotyping, expression of lncRNA and mRNA, cell proliferation, and cytokine production were tested by MassARRAY System, real-time PCR, CCK8, and ELISA.
A significant association with VKH was found for lnc-TOR3A-1:1/rs3829794, which is located in a non-HLA region (CC genotype: Bonferroni corrected P values [PC] = 2.98 × 10-8, odds ratio [OR] = 0.62; TT genotype: PC = 1.64 × 10-8, OR = 1.57; C allele: PC = 1.39 × 10-12, OR = 0.71). Additionally, an association was found for four lncRNA SNPs located in the HLA region. Functional experiments in rs3829794 genotyped individuals showed decreased ABL2 (ABL proto-oncogene 2, nonreceptor tyrosine kinase) expression, decreased proliferation of anti-CD3 plus anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs), and an increased production of IL-10 in CC carriers compared to TT carriers (P = 0.0073, P = 0.0011, and P = 0.002, respectively).
Our study identified five new loci associated with VKH susceptibility and identified a functional variant (lnc-TOR3A-1:1/rs3829794) that confers risk for VKH, which is possibly mediated by modulating gene expression, proliferation of lymphocytes, and regulation of anti-inflammatory cytokine production.
本研究旨在探讨长非编码 RNA（lncRNA）相关单核苷酸多态性（SNP）与 Vogt-小柳原田病（VKH）之间的关联。
通过多组学分析选择 lncRNA 相关 SNP。通过 MassARRAY 系统、实时 PCR、CCK8 和 ELISA 检测基因分型、lncRNA 和 mRNA 的表达、细胞增殖和细胞因子产生。
发现 lnc-TOR3A-1：1/rs3829794 与 VKH 显著相关，该 SNP 位于非 HLA 区域（CC 基因型：Bonferroni 校正 P 值 [PC] = 2.98×10-8，OR = 0.62；TT 基因型：PC = 1.64×10-8，OR = 1.57；C 等位基因：PC = 1.39×10-12，OR = 0.71）。此外，还发现了四个位于 HLA 区域的 lncRNA SNP 与 VKH 相关。在 rs3829794 基因型个体中进行的功能实验表明，ABL2（ABL 原癌基因 2，非受体酪氨酸激酶）表达降低，抗 CD3 加抗 CD28 刺激外周血单个核细胞（PBMCs）的增殖减少，CC 携带者的 IL-10 产生增加（P = 0.0073，P = 0.0011，P = 0.002）。
本研究鉴定了五个与 VKH 易感性相关的新位点，并鉴定了一个功能性变体（lnc-TOR3A-1：1/rs3829794），该变体可能通过调节基因表达、淋巴细胞增殖和调节抗炎细胞因子产生来增加 VKH 的风险。
