Expression of microRNA-146a and its clinical significance in primary gout arthritis

Abstract

Objective To investigate the role of miR-146a in the pathogenesis of primary gouty arthritis. Methods The subjects were divided into 4 groups: 55 acute gout patients (AG), 42 inter-critical gout patients (IG), 23 osteoarthritis patients (OA) and 43 healthy controls (HC). Clinical and laboratory parameters were also collected. The expression of miR-146a in the peripheral blood mononuclear cells (PBMCs) was detected using real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) (TaqMan probe). The PBMCs of HC were stimulated with monosodium urate (MSU 100 μg/ml) for 12 h, and then measured the interleukin-1β level, miR-146a, interleukin 1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) mRNA using enzyme linked immunosorbent assay (ELISA) and RT-qPCR respectively. SPSS 17.0 statistical software was used for analysis and the data were compared with Wilcoxon rank sum test and variance anaysis, and the gene expression level after stimulation of MSU was tested by t test. The correlation between the variables was analyzed using Spearman correlation analysis. Results ① The expression of miR-146a in the AG group was significantly decreased than that in the IG, OA and HC group (0.16±0.43 vs 0.26±0.54 vs 0.31±0.43 vs 0.29±0.36, P value was 0.05). ② In AG, the miR-146a level wasnegatively correlated with ESR (r=-0.355, P=0.031); and there was no significant correlation between the level of miR-146a and other laboratory data (P>0.05, respectively). ③ After stimulated with MSU in the PBMCs of HC, the expression of interleukin-1β was much higher than that in the control [(93±5) pg/ml vs (21±5) pg/ml; t=10.79, P<0.01], while the expression of miR-146a was much lower than that in the controls (0.248 ± 0.014 vs 0.528±0.046; t=5.76, P=0.000 4), TRAF6 mRNA was significantly increased than that in the controls (0.121 1±0.011 2 vs 0.024 3±0.002 0; t=8.744, P<0.01), however, no significant difference was observed with respect to IRAK1 mRNA level between the two groups [(0.090 ± 0.005) vs (0.079 ± 0.005); t=1.539, P=0.162]. Conclusion In acute gout attack, low expression of miR-146a may result in high IL-1β level; miR-146a may be a therapeutic target for gout inflammation brake. Key words: Arthritis, gouty; MicroRNAs; Interleukin-1; Interleukin-1 receptor-associated kinases; Tumor necrosis receptor-associated factor peptides and proteins