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Research On The Expression Of MicroRNA In Ankylosing Spondylitis

Posted on:2015-07-14Degree:MasterType:Thesis
Country:ChinaCandidate:Y LvFull Text:PDF
GTID:2284330467459198Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Ankylosing spondylitis (AS), which mainly involves the axial skeleton and thesacroiliac joint, is a chronic inflammatory spondyloarthropathy and characterized bysacroiliac joint and back pain along with ankylosis. Chinese people’s incidence rate isabout0.3%. Theetiology and pathogenesis of AS is unclear, it may be related to genetics,chronic inflammation, autoimmune disorders and other factors. Now that the T lymphocytedysfunction plays a central role in the pathogenesis of AS, especially helper T cells (Thcells), controlling the activity of lymphocyte and adaptive immune responses. Studiesindicate that miRNA plays a crucial role in establishing and maintaining the immuneregulation.Objective: To analyze the expression of microRNA inperipheral blood mononuclearcells (PBMC) of AS. Screening the miRNA related to AS, and predicted the target genesand performed by GO functional and KEGG pathway analysis, clearly signaling pathway,explore the role of miRNA in its pathogenesis.Methods: According to the standard of P <0.05difference and more than2timesfoldchange, we analysis of miRNA expression different between the AS patients andhealthy controls, using Solexa sequencing the whole genome scan, while using real-timequantitative PCR (qRT-PCR) method to validated the difference of miRNA in30ASpatients and healthy controls respectively. All patients meet the criteria of AmericanCollege of Rheumatology (ACR)1984modified New York criteria, meanwhile satisfyASpatients with the HLA-B27–positive, BASDAI>4.Results: The present study is firstly focus on microRNA expression in AS patients,which reveals that miRNA-1247-3p, miRNA-99a-5p, miRNA-501-3p, miRNA-146a-5pand miRNA-3168, miRNA-1260a, miRNA-1268a, miRNA-1908, miRNA-224-5P,miRNA-3614-5p, miRNA-548au-5p are decreased in PBMCs compared with healthy anddisease control individuals. Second we validated the eleven decreased miRNA in30casesand controls using qRT-PCRmethod. Meanwhile we found that all the target genes arefocus on ERAP1, STAT3, IGSF, IL17, IL2, IL22, IL23, IL24, IRAK, MAPK, TNF andTOLLIP, which have proven that they play a great role in AS pathegenesis. Conclusion:The eleven miRNA may influence the expression of ERAP1, STAT3,IGSF, IL17, IL2, IL22, IL23, IL24, IRAK, MAPK, TNF and TOLLIP gene, whichinvolved in the pathogenesis of AS. By measuring the expression of miRNA, it mayprovide a potential diagnostic marker for the early diagnosis of clinical AS.
Keywords/Search Tags:AS, RNA-Seq technology, miRNA
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