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

Objective: To evaluate the association between microRNA (miRNA) polymorphisms and rheumatoid arthritis (RA) susceptibility through meta-analysis. Methods: We systematically searched MEDLINE, EMBASE, and Web of Science for case-control studies examining five miRNA polymorphisms: miR-146a rs2910164, miR-499 rs3746444, miR-196a2 rs11614913, miR-155 rs767649, and miR-149 rs2292832. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Results: Twenty-three studies comprising 4,303 RA patients and 5,337 controls were included. Significant associations were identified for three polymorphisms. MiR-499 rs3746444 demonstrated increased RA risk across multiple genetic models (allelic, recessive, and homozygote). MiR-146a rs2910164 showed population-specific effects, conferring protection in Arabs (OR = 0.666, 95% CI = 0.520–0.853, p = 0.001) but not in Asian or European populations. The miR-149 rs2292832 A allele exhibited strong protective effects (OR = 0.314, 95% CI = 0.215–0.458, p < 0.001). No significant associations were observed for miR-196a2 rs11614913 or miR-155 rs767649 polymorphisms. Conclusions: This meta-analysis demonstrates that miRNA polymorphisms exhibit variable associations with RA susceptibility. MiR-499 rs3746444 increases risk, while miR-146a rs2910164 and miR-149 rs2292832 provide protection, with ethnic-specific effects for miR-146a rs2910164.