Pre—miR-146a基因rs2910164位点单核苷酸基因多态性及miR-146a表达与类风湿关节炎相关性研究  

Relationship between the single nucleotide polymorphisims in pre-miR-146a rs2910164 and expression of miR-146a in rheumatoid arthritis

作　　者：钱龙[1] 高登文[1] 汪国生[1] 李向培[1] 厉小梅[1] 陈杰[1] 秦明明[1] 

机构地区：[1]安徽医科大学附属省立医院风湿免疫科,合肥230001

出　　处：《中华微生物学和免疫学杂志》2012年第3期253-257,共5页Chinese Journal of Microbiology and Immunology

摘　　要：目的探讨pre—miR-146a基因rs2910164位点单核苷酸基因多态性及miR-146a表达与类风湿关节炎相关性。方法采用聚合酶链反应一连接酶检测反应检测123例类风湿关节炎（RA）患者和220例健康对照者pre—miR-146ars2910164位点基因多态性，应用实时荧光定量聚合酶链反应检测68例RA患者、10例骨关节炎（OA）患者及20例健康对照外周血单个核细胞中miR-146a的表达水平，并选取10例RA疾病活动患者行激素加免疫抑制剂正规治疗3个月后miR．146a表达水平的测定。收集并计算RA患者临床参数：发病年龄、性别、类风湿因子（RF）和抗环瓜氨酸肽（抗．CCP）抗体、RA疾病活动（DAS28≥3．2）、骨破坏（x〉I期）。统计学处理采用x2检验、方差分析、t检验和Pearson相关分析。结果RA组pre—miR-146ars2910164位点的基因型频率和等位基因频率与健康对照组比较，差异无统计学意义（P均〉0．05）。RA患者pre—miR-146ars2910164位点基因型与发病年龄、性别、RF和抗-CCP抗体阳性率、RA疾病活动、骨破坏阳性率及miR-146a表达量均无相关性（P均〉0．05）。RA患者组miR-146a的表达量高于健康对照组和OA组（P均〈0．01），后两组miR-146a的表达量无统计学差异（P〉0．05）。RA疾病活动组miR-146a表达高于非活动组和对照组（P均〈0．01），后两组miR-146a的表达量无统计学差异（P〉0．05）。RA疾病活动患者治疗后miR-146a表达下降（P〈0．05），DAS28评分降低（P〈0．01）。RA患者组miR-146a的表达与红细胞沉降率（ESR，即血沉）、C反应蛋白（CRP）及DAS28评分之间呈正相关（P均〈0．01），与RF、抗-CCP抗体滴度无相关性（P均〉0．05）。结论我国汉族人群中，pre—miR-146ars2910164位点多态性与RA的易感性、临床参数及miR-146a的表达无相关性，RA患者外周血单个核细胞miR-146a表达上调，其表达水平与RA病情活动有关，miR-146a�Objective To investigate the relationship between the single nucleotide polymorphisims in pre-miR-146a rs2910164 and miR-146a expression in rheumatoid arthritis（RA）. Methods Polymerase chain reactionligation detection reaction （PCR-LDR） was used to detect the pre-miR-146a rs2910164 single nucleotide polymorphisms in 123 patients with rheumatoid arthritis （RA） and 220 healthy controls. Expression of miR-146a in peripheral blood mononuclear ceils was studied using quantitative realtime polymerase chain reaction （qRT-PCR） in 68 RA patients, 10 osteoarthritis （OA） patients and 20 healthy controls. After application of glucocorticoid and NSAIDS combined with DMARDS for three months in 10 patients with active RA, miR-146a expression was again analyzed by qRT-PCR. Clinical characteris- tics including sex, age at onset, rheumatoid factor （RF）, anti-cyclic citrullinated peptide （anti-CCP） anti- body, RA activity （DAS28~〉3.2） and bone erosion（ X-ray 〉 I stage） were taken into account. ~2 test, One-Way ANOVA, t test and Pearson correlation were used for statistical analysis. Results The polymor- phisms of the pre-miR-146a rs2910164 were not correlated with susceptibility to RA （P〉0.05）. There were no associations between pre-miR-146a rs2910164 genotypes and sex, age at onset, status of RF and anti- CCP, RA activity, bone erosion and miR-146a expression in RA patients （P〉0.05 for each）. MiR-146a expression was significantly higher in RA patients than that in OA patients and that in healthy controls （P〈 0.01 for each） but did not differ between the latter two groups （P〉0.05）. MiR-146a expression was signifi- cantly higher in active RA patients than that in inactive patients and that in healthy individuals （P〈0.01 for each）. After treatment, miR-146a expression and DAS28 score were lower obviously （ P〈0.05, P〈0.01, respectively）. MiR-146a expression was positively correlated to ESR, CRP and DAS28 score （P〈0.01 for each）, but not to RF titer and

关 键 词：类风湿关节炎 MICRORNA MIR-146A 多态性 

分 类 号：R593.22[医药卫生—内科学]