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qingyun zhou, Aize Kijlstra; MicroRNA-146a and Ets-1 gene polymorphisms in ocular Behcet’s disease and Vogt-Koyanagi-Harada syndrome. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5386.
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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 Behcet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) disease in a Chinese Han population.
A total of 809 BD patients, 613 VKH patients 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 PBMCs by real-time PCR. Cytokine production by PBMCs were measured by ELISA.
A significantly decreased frequency of the homozygous rs2910164 CC genotype and C allele was observed in BD patients compared with controls (pca=1.24×10-5, odds ratio (OR) 0.61; pca=1.33×10-4, OR 0.75, respectively). MiR-146a expression in GG cases was 2.45-fold and 1.99-fold respectively higher than that in CC cases and GC cases. There was no association of other four 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. IL-17, 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 the IL-6 and 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 an decreased expression of miR-146a and certain proinflammatory cytokines in individuals carrying the CC genotype.
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