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Jian Qi, Liping Du, Jing Deng, Yang Qin, Guannan Su, Shengping Hou, Meng Lv, Qi Zhang, Aize Kijlstra, Peizeng Yang; Replication of Genome-Wide Association Analysis Identifies New Susceptibility Loci at Long Noncoding RNA Regions for Vogt-Koyanagi-Harada Disease. Invest. Ophthalmol. Vis. Sci. 2019;60(14):4820-4829. doi: https://doi.org/10.1167/iovs.19-27708.
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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.
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