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摘要
Polymorphisms located at microRNA (miRNA) binding sites may affect the expression of genes. The present study aimed to identify the association between an insertion/deletion (Ins/Del) polymorphism (rs3783553) in the 3'-untranslated region (3'-UTR) of interleukin-1 alpha (IL-1A) and the risk for osteoarthritis (OA). Using a luciferase reporter system, IL-1A was identified in the present study as an effective target gene of miR-122 in synovial cells that were obtained from patients who had received a synovectomy. This finding was verified further by the observation that exogenous over-expression of miR-122 in the synovial cells significantly downregulated the expression of IL-1A in the cells with Ins/Ins and Ins/Del genotypes, but not in the cells with Del/Del genotypes. Patients with OA (n=931) and OA-free volunteers (n=952) were enrolled in the study. Compared with the Del/Del genotype, patients possessing the Ins/Del or Ins/Ins genotype were associated with a lower risk for OA [odds ratio (OR)=0.67, P=0.0051; OR=0.65, P=0.0031, respectively], and the association was even stronger in young subjects (<62 years) (OR=0.53; P<0.001). Additionally, it was found that genotype was associated with radiographic severity (OR=0.72; P=0.023). The synovial fluid (SF) concentrations of IL-1A and miR-122 were measured in 75 OA patients. While the miR-122 concentrations were found to be comparable between each genotype group, the SF concentration of IL-1A in the Del/Del group was significantly higher than in the Ins/Del and Ins/Ins genotype groups. Therefore, the present study identified that the Ins/Del polymorphism in the 3'-UTR of IL-1A may affect genetic expression and, to the best of our knowledge, is the first study to demonstrate that the minor allele (Del) is associated with an elevated risk for OA and disease severity.
- 出版日期2015-10
- 单位大连大学
