國家衛生研究院 NHRI:Item 3990099045/13856
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    题名: Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis
    作者: Tseng, CC;Lin, YZ;Lin, CH;Hwang, DY;Li, RN;Tsai, WC;Ou, TT;Wu, CC;Lin, YC;Sung, WY;Chen, KY;Chang, SJ;Yen, JH
    贡献者: National Institute of Cancer Research
    摘要: BACKGROUND: Genetic and epigenetic factors are strongly associated with the autoimmune disease rheumatoid arthritis (RA). Cyclic AMP response element modulator (CREM), a gene related to immune system regulation, has been implicated in various immune-mediated inflammatory processes, although it remains unknown whether CREM is involved in RA. METHODS: This study enrolled 278 RA patients and 262 controls. Three variants [rs12765063, rs17499247, rs1213386] were identified through linkage disequilibrium and expression quantitative trait locus analysis, and CREM transcript abundance was determined by quantitative real-time polymerase chain reaction. The identified variants were genotyped using the TaqMan Allelic Discrimination assay, and CREM promoter methylation was assessed by bisulfite sequencing. Differences between groups and correlations between variables were assessed with Student's t-tests and Pearson's correlation coefficients. Associations between phenotypes and genotypes were evaluated with logistic regression. RESULTS: RA patients exhibited increased CREM expression (P < 0.0001), which was decreased by methotrexate (P = 0.0223) and biologics (P = 0.0001), but could not be attributed to CREM variants. Interestingly, rs17499247 displayed a significant association with serositis (P = 0.0377), and rs1213386 increased the risk of lymphadenopathy (P = 0.0398). Furthermore, seven CpG sites showed decreased methylation in RA (P = 0.0477~ P < 0.0001). CONCLUSIONS: Collectively, our results indicate that CREM hypomethylation and CREM upregulation occur in RA and that CREM variants are involved in the development of serositis and lymphadenopathy in RA. This study highlights the novel roles of CREM in RA pathophysiology.
    日期: 2021-11-16
    關聯: European Journal of Clinical Investigation. 2021 Nov 16;Article number e13715.
    Link to: http://dx.doi.org/10.1111/eci.13715
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-2972&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000770831000001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85126559330
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