Genetic variant in microRNA-146a gene is associated with risk of rheumatoid arthritis

Lin-Lin Zhang1,2, Xiao-Xiao Wu1,2, Xu-Fan Wang1,2

  • 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, PR China.

Annals of Medicine
|June 1, 2021
PubMed
Abstract

Insights

Single nucleotide polymorphisms (SNPs) in the microRNA-146a (miR-146a) gene are associated with rheumatoid arthritis (RA) risk. The study identified a specific SNP, rs2431697, as increasing susceptibility to RA, particularly in Asian populations.

Area of Science:

  • Genetics
  • Immunology
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex genetic component.
  • MicroRNA-146a (miR-146a) plays a role in immune regulation and has been implicated in various inflammatory conditions.
  • The association between specific single nucleotide polymorphisms (SNPs) in the miR-146a gene and RA susceptibility requires further investigation.

Purpose of the Study:

  • To investigate the association between SNPs in the miR-146a gene and the susceptibility to rheumatoid arthritis (RA).
  • To identify specific miR-146a variants that may influence RA risk.
  • To explore the functional implications of identified variants in relation to RA pathogenesis.

Main Methods:

  • Systematic extraction of genetic data for miR-146a from existing genome-wide association studies (GWASs) on RA.
  • Conducting a replication study in an independent Chinese cohort to validate findings for selected variants.
  • Performing a meta-analysis combining GWAS data with the replication study results.
  • Utilizing epigenetic annotation and cytokine assays to explore potential variant functions.

Main Results:

  • Genetic association data from three GWASs indicated that the T allele of the functional SNP rs2431697 increases RA susceptibility.
  • The association of SNP rs2431697 with RA was confirmed in the Chinese replication cohort (OR = 1.24, 95% CI = 1.06-1.46, p = 8.69E-03).
  • The effect size of rs2431697 was larger in Asian populations compared to European populations (Asian meta-analysis: OR = 1.15, 95% CI = 1.09-1.22, p = 4.37E-07).
  • The risk allele T of rs2431697 was inversely associated with plasma TNF-α levels in healthy controls (p = 0.016).

Conclusions:

  • Genetic variants within the miR-146a gene are associated with an increased risk of rheumatoid arthritis.
  • The SNP rs2431697 in the miR-146a gene is a significant risk factor for RA susceptibility.
  • These findings contribute to understanding the genetic underpinnings of RA and highlight miR-146a as a potential player in its pathogenesis.

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