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中华临床医师杂志(电子版) ›› 2021, Vol. 15 ›› Issue (06) : 418 -428. doi: 10.3877/cma.j.issn.1674-0785.2021.06.004

临床研究

miR-146a和miR-499多态性与类风湿性关节炎易感性的Meta分析
张越琳1, 曹家铭1, 刘惠媛1, 王俏1, 付凌雨2,†()   
  1. 1. 110001　沈阳，中国医科大学附属第一医院临床流行病与循证医学教研室
    2. 110001　沈阳，中国医科大学附属第一医院临床流行病与循证医学教研室；病案管理中心
  • 收稿日期:2021-04-26 出版日期:2021-06-15
  • 通信作者: 付凌雨

Association of miR-146a and miR-499 polymorphisms with susceptibility to rheumatoid arthritis: a Meta-analysis

Yuelin Zhang1, Jiaming Cao1, Huiyuan Liu1, Qiao Wang1, Lingyu Fu2,†()   

  1. 1. Department of Clinical Epidemiology and Evidence-based Medicine
    2. Department of Clinical Epidemiology and Evidence-based Medicine; Medical Record Management Center, the First Affiliated Hospital, China Medical University, Shenyang 110001, China
  • Received:2021-04-26 Published:2021-06-15
  • Corresponding author: Lingyu Fu
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引用本文：

张越琳, 曹家铭, 刘惠媛, 王俏, 付凌雨. miR-146a和miR-499多态性与类风湿性关节炎易感性的Meta分析[J]. 中华临床医师杂志(电子版), 2021, 15(06): 418-428.

Yuelin Zhang, Jiaming Cao, Huiyuan Liu, Qiao Wang, Lingyu Fu. Association of miR-146a and miR-499 polymorphisms with susceptibility to rheumatoid arthritis: a Meta-analysis[J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(06): 418-428.

目的

采用Meta分析的方法评价研究microRNAs基因多态性与类风湿性关节炎（RA）的相关性。

方法

系统检索维普数据库、万方数据库、中国生物医学文献数据库、CNKI、PubMed、Cochrane、Embase数据库，检索microRNAs基因多态性与RA相关研究，检索时限为建库至2020年5月1日。同时手工检索主题相关综述的参考文献纳入符合标准的研究并进行数据提取和质量评价。采用Stata 15.1软件进行Meta分析。

结果

共纳入14项队列研究，涉及1945例RA病例和2405例对照。Meta分析结果显示：RA患者miR-146a的G/G基因型表达量显著高于正常人［OR=1.15，95%CI（1.00，1.33），P=0.048］，其他表型与RA患者发病风险无显著相关［C/C：OR=0.94，95%CI（0.83，1.07），P=0.353；G/C：OR=0.92，95%CI（0.82，1.03），P=0.135］。RA患者miR-499的C/T基因型显著低于正常人［OR=0.84，95%CI（0.72，1.00），P=0.044］，其他基因型与正常人相比不存在显著差异［T/T：OR=0.97，95%CI（0.77，1.24），P=0.831；C/C：OR=1.40，95%CI（0.96，2.05），P=0.713］。按人种进行亚组分析，在高加索人群及亚洲人群中，miR-146a与miR-499基因多态性与RA患者发病之间的关联性均无统计学意义（P＞0.05）。

结论

miR-146a的G/G基因型和miR-499的C/T基因型与人群RA的遗传易感性有关。

关键词: 微小RNA, 类风湿性关节炎, 基因多态性, Meta分析
Objective

To evaluate the association between microRNA gene polymorphisms and rheumatoid arthritis (RA) using Meta-analysis.

Methods

A systematic search of Chinese biomedical literature database, VIP database, Wanfang data, CNKI, PubMed, Cochrane, and Embase database was performed to identify articles reporting on the association between microRNA gene polymorphisms and RA. The search time limit was from the inception of the database to May 1, 2020. The references of retrieved articles were manually searched to ensure the comprehensiveness of the retrieval. Studies meeting the inclusion criteria were included to conduct data extraction and quality evaluation. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. A Meta-analysis was performed using Stata 15.1 software.

Results

A total of 14 cohort studies were included, involving 1945 RA cases and 2405 controls. Meta-analysis results showed that the expression level of G/G genotype of miR-146a in RA patients was significantly higher than that in normal controls [OR=1.15, 95%CI (1.00, 1.33), P=0.048], other phenotypes were not significantly associated with the risk of RA [C/C: OR=0.94, 95%CI (0.83, 1.07), P=0.353; G/C: OR=0.92, 95%CI(0.82,1.03), P=0.135]. The C/T genotype of miR-499 in RA patients was significantly lower than that in normal controls [OR=0.84, 95%CI (0.72,1.00), P=0.044], there were no significant differences in other genotypes [T/T: OR=0.97, 95%CI (0.77,1.24), P=0.831; C/C: OR=1.40, 95%CI (0.96,2.05), P=0.713]. Analysis of subgroups by race showed that there was no statistically significant association between the polymorphisms of miR-146a and miR-499 and the incidence of RA in Caucasian and Asian populations (P＞0.05).

Conclusion

This study find that the G/G genotype of miR-146a and C/T genotype of miR-499 are related to genetic susceptibility to RA.

Key words: MicroRNA, Rheumatoid arthritis, Gene polymorphism, Meta-analysis
图1 文献筛选流程及结果
表1 纳入14篇文献基本信息情况
编号 作者 年份（年） 国家 研究方法 样本量（例）

RA患者年龄

（岁，

x¯
±s）

 RA患者性别（例，男/女） 微小RNA 结局指标
RA组 对照组
1 Fattah et al［17］ 2018 埃及 队列研究 100 100 41.7±8.5 14/86 miR-499 1、2、3
2 高登文等［18］ 2012 中国 队列研究 123 220 49±13 18/105 miR-146a 4、5、6
3 Zhang et al［19］ 2013 中国 队列研究 214 478 54.63±15.77 61/153 miR-499 1、2、3
4 Bogunia-Kubik et al［20］ 2016 波兰 队列研究 111 130 - - miR-146a 4、5、6
5 Ayeldeen et al［21］ 2018 埃及 队列研究 52 56 39.0±10.7 -

miR-499、

miR-146a

 1、2、3、4、5、6
6 Ciccacci et al［22］ 2016 意大利 队列研究 192 298 54.1±13.2 45/147 miR-146a 4、5、6
7 Hassine et al［23］ 2017 突尼斯 队列研究 165 150 - - miR-146a 4、5、6
8 谢传美等［24］ 2018 中国 队列研究 600 398 41.4±5.9 134/466

miR-499、

miR-146a

 1、2、3、4、5、6
9 肖茗渊等［25］ 2015 中国 队列研究 200 120 49.0±12.9 30/170 miR-499 1、2、3
10 Chatzikyriakidou et al［26］ 2010 希腊 队列研究 136 147 60.8±12.7 27/109 miR-146a 4、5、6
11 El-Shal et al［27］ 2013 埃及 队列研究 217 245 38.4±7.0 -

miR-499、

miR-146a

 1、2、3、4、5、6
12 Alemán-Ávila et al［28］ 2017 墨西哥 队列研究 412 486 51.8±13.6 34/378 miR-499 1、2、3
13 Yang et al［29］ 2010 中国 队列研究 208 240 48±13 36/172

miR-499、

miR-146a

 1、2、3、4、5、6
14 Zhou et al［30］ 2015 中国 队列研究 615 839 54.5±15.2 143/472 miR-146a 4、5、6
表2 文献质量评估
作者 年份（年） 研究人群选择 组间可比性

暴露因素的

测量

 得分（分）
Fattah et al［17］ 2018 ☆☆☆ ☆☆ ☆☆☆ 8
高登文等［18］ 2012 ☆☆☆ ☆☆ ☆☆☆ 8
Zhang et al［19］ 2013 ☆☆ ☆☆ ☆☆☆ 7
Bogunia-Kubik et al［20］ 2016 ☆☆☆ ☆☆ ☆☆☆ 8
Ayeldeen et al［21］ 2018 ☆☆☆ ☆☆ ☆☆ 7
Ciccacci et al［22］ 2016 ☆☆☆ ☆☆ ☆☆☆ 8
Hassine et al［23］ 2017 ☆☆ ☆☆ ☆☆☆ 7
谢传美等［24］ 2018 ☆☆☆ ☆☆ ☆☆ 7
肖茗渊等［25］ 2015 ☆☆☆ ☆☆ ☆☆☆ 8
Chatzikyriakidou et al［26］ 2010 ☆☆ ☆☆ ☆☆☆ 7
El-Shal et al［27］ 2013 ☆☆☆ ☆☆ ☆☆☆ 8
Alemán-Ávila et al［28］ 2017 ☆☆☆ ☆☆ ☆☆☆ 8
Yang et al［29］ 2010 ☆☆ ☆☆ ☆☆☆ 7
Zhou et al［30］ 2015 ☆☆ ☆☆ ☆☆☆ 7
图2 C/T（miR-499）与类风湿关节炎相关性的森林图
图3 T/T（miR-499）与类风湿关节炎相关性的森林图
图4 C/C（miR-499）与类风湿关节炎相关性的森林图
图5 C/C（miR-146a）与类风湿关节炎相关性的森林图
图6 G/C（miR-146a）与类风湿关节炎相关性的森林图
图7 G/G（miR-146a）与类风湿关节炎相关性的森林图
图8 C/C（miR-146a）与类风湿关节炎相关性的漏斗图
图9 G/C（miR-146a）与类风湿关节炎相关性的漏斗图
图10 G/G（miR-146a）与类风湿关节炎相关性的漏斗图
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