A functional variant of pre-miRNA-196a2 confers risk for Behcet's disease but not for Vogt-Koyanagi-Harada syndrome or AAU in ankylosing spondylitis.
This study aimed to investigate the predisposition of common pre-miRNA SNPs with Behcet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS). A two-stage association study was carried out in 859 BD, 400 VKH syndrome, 209 AAU(+)AS(+) patients and 1,685 controls all belonging to a Chinese Han population. Genotyping, the expression of miR-196a and Bach1 (the target gene of miR-196a), cell proliferation, cytokine production were examined by PCR-RFLP, real-time PCR, CCK8 and ELISA. In the first stage study, the results showed significantly increased frequencies of the miR-196a2/rs11614913 TT genotype and T allele in BD patients (adjusted P(c) = 0.024, OR = 1.63; adjusted P(c) = 5.4 × 10(-3), OR = 1.45, respectively). However, no significant association of the tested SNPs with VKH and AAU(+)AS(+) patients was observed. The second stage and combined studies confirmed the association of rs11614913 with BD (TT genotype: adjusted P(c) = 6×10(-5), OR = 1.53; T allele: adjusted P(c) = 8×10(-6), OR = 1.35; CC genotype: adjusted P(c) = 0.024, OR = 0.68). A stratified analysis showed an association of the rs11614913 TT genotype and T allele with the arthritis subgroup of BD (P(c) = 5.3 × 10(-3), OR = 1.89; P(c) = 0.015, OR = 1.56, respectively). Functional experiments showed a decreased miR-196a expression, an increased Bach1 expression and an increased production of IL-1β and MCP-1 in TT cases compared to CC cases (P = 0.023, P = 0.0073, P = 0.012, P = 0.002, respectively). This study shows that a functional variant of miR-196a2 confers risk for BD but not for VKH syndrome or AAU(+)AS(+) by modulating the miR-196a gene expression and by regulating pro-inflammatory IL-1β and MCP-1 production.
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, 400016, People's Republic of China.
Jian
J
Qi
Shengping
S
Hou
Qi
Q
Zhang
Dan
D
Liao
Lin
L
Wei
Jing
J
Fang
Yan
Y
Zhou
Aize
A
Kijlstra
Peizeng
P
Yang
D000208:Acute Disease; D001528:Behcet Syndrome / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012322:RNA Precursors / Q000235:genetics; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D014606:Uveitis, Anterior / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D014607:Uveomeningoencephalitic Syndrome / Q000453:epidemiology / Q000235:genetics*
C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D012322:RNA Precursors