类风湿关节炎患者血浆miR-146a表达及基因高甲基化与疾病活动程度的关系  

Relationship between the plasma miR- 146a expression, gene hypermethylation and the disease activity in patients with rheumatoid arthritis

作　　者：庞琳烜 杨西超 李治琴 杜望磊 PANG Linxuan;YANG Xichao;LI Zhiqin;DU Wanglei(Department of Clinical Immunology,the First Affiliated Hospital of Air Force Military Medical University,Xi’an 710032,China)

机构地区：[1]空军军医大学第一附属医院临床免疫科,陕西西安710032

出　　处：《东南大学学报（医学版）》2022年第6期818-824,共7页Journal of Southeast University(Medical Science Edition)

基　　金：陕西省重点研发计划项目(2021SF-074)。

摘　　要：目的:探讨类风湿关节炎(RA)患者血浆微小RNA(miRNA)-146a表达及基因高甲基化与疾病活动程度的关系。方法:2019年3月至2020年4月在我院临床免疫科招募122例RA患者为RA组,基于血细胞沉降率(ESR)获得28个关节疾病活动评分(DAS28-ESR)测量疾病活动性;另纳入同期健康志愿者141例为对照组。采用实时荧光定量PCR法检测血浆miR-146a水平,实时荧光定量甲基化特异性PCR(qMSP)分析甲基化状态。结果:RA组患者血浆miR-146a水平显著高于对照组,miR-146a基因甲基化水平显著低于对照组(P<0.05)。血浆miR-146a水平与miR-146a基因甲基化水平呈负相关(P<0.05)。随疾病活动程度的增加,RA患者血浆miR-146a水平呈升高趋势,miR-146a基因甲基化水平呈下降趋势(P<0.05)。血浆miR-146a水平与DAS28-ESR评分、ESR、C反应蛋白水平、关节肿胀计数、关节压痛计数、患者主观总体评估、医生总体评估、简化疾病活动指数呈正相关(P<0.05);miR-146a基因甲基化水平与上述指标呈负相关(P<0.05)。结论:血浆miR-146a及基因甲基化状态与RA患者疾病活动程度有关,有望作为诊断和控制RA疾病活动的潜在标志物。Objective: To investigate the relationship between the plasma microRNA(miRNA)-146a expression, gene hypermethylation and the disease activity in patients with rheumatoid arthritis(RA). Methods: From March 2019 to April 2020, 122 RA patients were recruited into RA group in the rheumatology department of our hospital. The disease activity was measured using the 28-joint disease activity score obtained on the basis of erythrocyte sedimentation rate(ESR)(DAS28-ESR). During the same period, another 141 healthy volunteers were included as control group. The plasma miR-146a level was detected by real-time fluorescence quantitative PCR,and the methylation status was analyzed by real-time fluorescence quantitative methylation specific PCR(qMSP). Results: The plasma miR-146a level in the RA group was significantly higher than that in the control group, and the methylation level of miR-146a gene was significantly lower than that in the control group(P<0.05). Plasma miR-146a level was negatively correlated with miR-146a gene methylation level(P<0.05). With the increase of disease activity, the plasma level of miR-146a increased and the methylation level of miR-146a gene decreased(P<0.05). The plasma miR-146a level was positively correlated with DAS28-ESR, ESR, C-reactive protein, joint swelling count, joint tenderness count, patients’ subjective global assessment, physician’s global assessment and simplified disease activity index(P<0.05). The methylation level of miR-146a gene was negatively correlated with the above indexes(P<0.05). Conclusion: Plasma miR-146a and gene methylation status are related to the degree of disease activity in RA patients and may be potential markers for the diagnosis and control of RA disease activity.

关 键 词：类风湿关节炎 微小RNA-146a 甲基化 疾病活动程度 

分 类 号：R593.22[医药卫生—内科学]