An Updated Meta-Analysis of the Associations Between MicroRNA Polymorphisms and Susceptibility to Rheumatoid Arthritis.

Mi Zhou,Mao Xiong,Xin Zhu,Bo Jiang

doi:10.3389/fphys.2018.01604

Abstract

Aims: Rheumatoid arthritis (RA) is characterized by cartilage and bone damage leading to disability. Here, the association between microRNA (miRNA) polymorphisms and susceptibility to RA was evaluated by performing an updated meta-analysis and systematic review.Main methods: An electronic search of databases including PubMed and Embase was performed from inception to December 8, 2017 to retrieve studies investigating the association between miRNA polymorphisms and RA risk. Two reviewers independently screened literature according to the inclusion and exclusion criteria and extracted data. The meta-analysis was conducted using Stata 14.0 software.Key findings: Thirteen case-control studies with 2660 cases and 4098 controls were screened out after a systematic search. One study from the miR-146a rs2910164 G > C polymorphism group and two from the miR-499 rs3746444 T > C polymorphism group were excluded because of deviations from Hardy-Weinberg equilibrium. Pooled analysis demonstrated that miR-146a rs2910164 G > C polymorphism was not significantly associated with susceptibility to RA. However, a significant association was observed between miR-499 rs3746444 T > C polymorphism and RA risk (C vs. T: OR = 1.22, 95% CI = 1.05–1.42, P = 0.008; TC vs. TT: OR = 1.26, 95% CI = 1.05–1.50, P = 0.011; TC/CC vs. TT: OR = 1.26, 95% CI = 1.07–1.5, P = 0.007). Subgroup analysis based on ethnicity showed no significant association between miR-499 T > C polymorphism and susceptibility to RA in the Asian population (P > 0.05). However, in Caucasian population, the C allele in the miR-499 T > C polymorphism was a contributor to RA susceptibility in some genetic models (C vs. T: OR = 1.64, 95% CI = 1.28–2.11, P < 0.001; TC vs. TT: OR = 1.95, 95% CI = 1.40–2.71, P < 0.001; TC/CC vs. TT: OR = 1.96, 95% CI = 1.43–2.69, P < 0.001).Significance: The miR-146a rs2910164 G > C polymorphism was not associated with susceptibility to RA. In the Caucasian population, the C allele in the miR-499 T > C polymorphism contributed to RA susceptibility.

Highlights

Rheumatoid arthritis (RA), one of the most prevalent chronic inflammatory diseases, is characterized by damage to cartilage and bone leading to disability (Smolen et al, 2016)
The inclusion criteria of our meta-analysis were as follows: (1) case-control studies; (2) investigation of miRNA polymorphisms and RA susceptibility; (3) detailed numbers of alleles and genotypes between cases and controls; (4) full text published in English; (5) control group consistent with Hardy-Weinberg Equilibrium (HWE); and (6) any specific miRNA with at least two case-control studies to evaluate the association between single nuclear polymorphism and RA susceptibility
A total of 13 articles with 2660 cases and 4098 controls were included in the meta-analysis (Chatzikyriakidou et al, 2010; Yang et al, 2011, 2016; Jimenez-Morales et al, 2012; El-Shal et al, 2013; Hashemi et al, 2013; Zhang et al, 2013; Zhou X. et al, 2015; Bogunia-Kubik et al, 2016; Ciccacci et al, 2016; Toraih et al, 2016; Fattah et al, 2017; Hassine et al, 2017)

Summary

Introduction

Rheumatoid arthritis (RA), one of the most prevalent chronic inflammatory diseases, is characterized by damage to cartilage and bone leading to disability (Smolen et al, 2016). It is a substantial burden for individuals and society, with up to 0.5% of the global population affected (Neogi et al, 2010), and the identification of novel therapeutic strategies to control inflammation and reduce severe consequences is increasingly imperative. MiRNAs play a significant role in regulating biological processes, including proliferation, apoptosis, and development (Esteller, 2011)

Methods

Results

Discussion

Conclusion