TY - JOUR
T1 - Replication of Genome-Wide Association Analysis Identifies New Susceptibility Loci at Long Noncoding RNA Regions for Vogt-Koyanagi-Harada Disease
AU - Qi, Jian
AU - Du, Liping
AU - Deng, Jing
AU - Qin, Yang
AU - Su, Guannan
AU - Hou, Shengping
AU - Lv, Meng
AU - Zhang, Qi
AU - Kijlstra, Aize
AU - Yang, Peizeng
PY - 2019/11
Y1 - 2019/11
N2 - PURPOSE. This study was aimed at investigating the association of long noncoding RNA (LncRNA)-related single nucleotide polymorphisms (SN'Ps) with Vogt-Koyanagi-Harada disease.METHODS. 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.RESULTS. 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 [P-C] = 2.98 x 10(-8), odds ratio [OR] = 0.62; TT genotype: P-C = 1.64 x 10(-8), OR = 1.57; C allele: P-C = 1.39 x 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 IT carriers (P = 0.0073, P = 0.0011, and P = 0.002, respectively).CONCLUSIONS. 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.
AB - PURPOSE. This study was aimed at investigating the association of long noncoding RNA (LncRNA)-related single nucleotide polymorphisms (SN'Ps) with Vogt-Koyanagi-Harada disease.METHODS. 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.RESULTS. 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 [P-C] = 2.98 x 10(-8), odds ratio [OR] = 0.62; TT genotype: P-C = 1.64 x 10(-8), OR = 1.57; C allele: P-C = 1.39 x 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 IT carriers (P = 0.0073, P = 0.0011, and P = 0.002, respectively).CONCLUSIONS. 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.
KW - lncRNA
KW - Vogt-Koyanagi-Harada disease
KW - multi-omics analysis
KW - BEHCETS-DISEASE
KW - GENE POLYMORPHISMS
KW - VKH SYNDROME
KW - T-CELLS
KW - EXPRESSION
KW - SNPS
KW - SENSITIZATION
KW - RECOGNITION
KW - VARIANTS
KW - DATABASE
U2 - 10.1167/iovs.19-27708
DO - 10.1167/iovs.19-27708
M3 - Article
C2 - 31747682
VL - 60
SP - 4820
EP - 4829
JO - Investigative Ophthalmology & Visual Science
JF - Investigative Ophthalmology & Visual Science
SN - 0146-0404
IS - 14
ER -