基因多态性对托法替布联合艾拉莫德治疗中重度类风湿关节炎疗效的影响 点击下载
论文标题： 基因多态性对托法替布联合艾拉莫德治疗中重度类风湿关节炎疗效的影响
英文标题：
中文摘要： 目的 探讨MIR149rs2292832与MIR499rs3746444基因多态性对托法替布联合艾拉莫德治疗中重度类风湿关节炎（RA）疗效的影响，为中重度RA患者的个体化治疗提供遗传学参考。方法本研究为前瞻性队列研究，根据基因分型检测结果进行分组。纳入2023年1月至2024年1月在我院免疫科确诊的中重度RA患者320例，所有患者规律接受托法替布（5mg，每日2次）联合艾拉莫德（25mg，每日2次）治疗，疗程为24周。比较不同基因型患者的临床疗效，包括美国风湿病学会（ACR）20/50/70应答、基于C反应蛋白的28关节疾病活动度评分（DAS28-CRP）、红细胞沉降率（ESR）、C反应蛋白（CRP）等，同时开展联合基因型分析及多因素Logistic回归分析。结果MIR149rs2292832CC型患者ACR20、ACR50、ACR70应答率（88.90%、67.78%、45.56%）均显著高于CT型和TT型（P＜0.05）；治疗24周后，CC型患者DAS28-CRP下降值、ESR下降值、CRP下降值均显著高于CT型和TT型（P＜0.05），CC型患者24周DAS28-CRP显著低于CT型和TT型（P＜0.05）。MIR499rs3746444GG型患者ACR20、ACR50、ACR70应答率（91.46%、73.17%、52.44%）均显著高于AG型和AA型（P＜0.05）；治疗24周后，GG型患者DAS28-CRP下降值、ESR下降值、CRP下降值均显著高于AG型和AA型（P＜0.05），GG型患者24周DAS28-CRP显著低于AG型和AA型（P＜0.05）。在9组联合基因型中，CC+GG型患者的疗效最优。MIR149rs2292832CC基因型和MIR499rs3746444GG基因型是临床缓解的独立预测因素（P＜0.01）；基线DAS28-CRP≥6.5分是临床缓解的负向预测因子（P＜0.05）。结论MIR149rs2292832与MIR499rs3746444基因多态性显著影响托法替布联合艾拉莫德治疗中重度RA的疗效，携带CC、GG基因型的患者应答更优。
英文摘要： OBJECTIVE To investigate the effects of MIR149 rs2292832 and MIR499 rs3746444 gene polymorphisms on the efficacy of tofacitinib combined with iguratimod in the treatment of moderate‑to‑severe rheumatoid arthritis （RA）， to provide genetic reference for individualized treatment of moderate‑to‑severe RA patients.METHODS This was a prospective cohort study， and patients were grouped according to genotyping results. A total of 320 patients with moderate-to-severe RA diagnosed in the department of immunology of our hospital between January 2023 and January 2024 were enrolled. All patients received standardized treatment with tofacitinib （5 mg twice daily） combined with iguratimod （25 mg twice daily） for 24 weeks treatment course. Clinical efficacy outcomes， including American College of Rheumatology （ACR） 20/50/70 responses， disease activity score‑28 based on C‑reactive protein （DAS28-CRP）， erythrocyte sedimentation rate （ESR） and C-reactive protein （CRP）， were compared among patients with different genotypes. Combined-genotype analysis and multivariate Logistic regression analysis were also performed.RESULTS The MIR149 rs2292832 CC-genotype patients exhibited significantly higher ACR20， ACR50 and ACR70 response rates （88.90%， 67.78%， 45.56%） than those carrying CT- and TT-genotypes （ P ＜0.05）. After 24 weeks treatment， the reductions in DAS28‑CRP， ESR and CRP were significantly greater in CC‑genotype patients than in CT‑ and TT‑genotype patients （ P ＜0.05）， and the 24‑week DAS28‑CRP was significantly lower in the CC‑genotype patients than in CT‑ and TT‑genotype patients （ P ＜0.05）. The MIR499 rs3746444 GG-genotype showed significantly higher ACR20， ACR50 and ACR70 response rates （91.46%， 73.17%， 52.44%） than those carrying AG‑ and AA‑genotypes （ P ＜0.05）. After 24 weeks of treatment， the reductions in DAS28‑CRP， ESR and CRP were significantly greater in GG‑genotype patients than in AG- and AA-genotype patients and the 24‑weeks DAS28‑CRP was significantly lower in the GG‑genotype patients than in AG- and AA-genotype patients （ P ＜0.05）. Among the nine combined‑genotyps， the CC+GG genotype yielded the best treatment response. The MIR149 rs2292832 CC and MIR499 rs3746444 GG genotypes were independent predictors of clinical remission （ P ＜0.01）， whereas baseline DAS28‑CRP ≥ 6.5 served as a negative predictor of clinical remission （ P ＜0.05）.CONCLUSIONS Gene polymorphisms of MIR149 rs2292832 and MIR499 rs3746444 significantly influence the therapeutic effect of tofacitinib combined with iguratimod in patients with moderate-to-severe RA. Patients carrying CC and GG genotypes achieve better treatment responses.
期刊： 2026年第37卷第17期
作者： 史俊；赵阳；胡荣雪；刘姗姗；贾彬；徐建萍；田佩华
英文作者： SHI Jun，ZHAO Yang，HU Rongxue，LIU Shanshan，JIA Bin，XU Jianping，TIAN Peihua
关键字： 类风湿关节炎；MIR149；MIR499；基因多态性；托法替布；艾拉莫德
KEYWORDS： MIR149 ; MIR499 ;gene polymorphism;tofacitinib;iguratimod
总下载数： 81次
本日下载数： 2次
本月下载数： 81次
文件大小： 619.60Kb

* 注：未经本站明确许可，任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作！