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Association between miRNA polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis

Young Ho Lee1, Gwan Gyu Song1

  • 1Department of Rheumatology, Korea University College of Medicine, Seoul, Korea.

Biomarkers in Medicine
|October 21, 2025
PubMed
Abstract

Insights

This meta-analysis reveals that microRNA (miRNA) polymorphisms have varied links to rheumatoid arthritis (RA) susceptibility. Certain miRNA polymorphisms increase RA risk, while others offer protection, with some showing ethnic-specific effects.

Area of Science:

  • Genetics
  • Immunology
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) is an autoimmune disease with a complex genetic component.
  • MicroRNAs (miRNAs) are small non-coding RNAs that play crucial roles in gene regulation and have been implicated in various diseases, including RA.
  • Genetic variations in miRNA genes (polymorphisms) may influence miRNA function and contribute to disease susceptibility.

Purpose of the Study:

  • To conduct a meta-analysis evaluating the association between specific miRNA polymorphisms and rheumatoid arthritis (RA) susceptibility.
  • To identify which miRNA polymorphisms are significantly associated with RA risk or protection.

Main Methods:

  • Systematic literature search of MEDLINE, EMBASE, and Web of Science for relevant case-control studies.
  • Inclusion of studies examining five specific miRNA polymorphisms: miR-146a rs2910164, miR-499 rs3746444, miR-196a2 rs11614913, miR-155 rs767649, and miR-149 rs2292832.
  • Calculation of odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models to assess the strength of associations.

Main Results:

  • Twenty-three studies with 4,303 RA patients and 5,337 controls were analyzed.
  • MiR-499 rs3746444 was significantly associated with increased RA risk across multiple genetic models.
  • MiR-146a rs2910164 showed protective effects in Arab populations but not in Asian or European populations.
  • MiR-149 rs2292832 exhibited strong protective effects against RA.
  • No significant associations were found for miR-196a2 rs11614913 or miR-155 rs767649.

Conclusions:

  • MiRNA polymorphisms display heterogeneous associations with RA susceptibility.
  • MiR-499 rs3746444 is a risk factor for RA, whereas miR-146a rs2910164 and miR-149 rs2292832 are protective.
  • The protective effect of miR-146a rs2910164 is population-specific, highlighting the importance of ethnic background in genetic association studies of RA.
Keywords:
MicroRNAsautoimmune diseasegene expression regulationgenetic association studygenetic predisposition to diseaseinflammatory responsemeta-Analysispolymorphismrheumatoid arthritissingle nucleotide polymorphism

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