Exploring the Associations and Molecular Impacts of miR-146a/rs2910164 and miR-196a2/rs185070757 with Rheumatoid Arthritis in a Pakistani Population

Introduction: MicroRNAs (miRNAs) are a new class of molecules that participate in post-transcriptional regulation of gene expression and hence have been reported to have a crucial role in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the association of miR-146a rs2910164 (G/C) and miR-196a2 rs185070757 (T/G) with RA susceptibility in Pakistani patients and to bioinformatically predict the molecular function of these miRNAs.Methods: A case-control study on 600 individuals was conducted, including 300 RA patients and 300 matching healthy controls. Genotyping was performed by tetra-primer amplification of refractory mutation system-polymerase chain reaction, and the association between variants and RA was statistically determined using different models.Results: For the variant rs2910164 (G/C) in miR-146a, no difference in genotype distribution was observed between RA cases and controls, as determined using co-dominant (chi(2) = 4.33; p = 0.114), homozygous dominant (C/C vs. G/G + C/G) (OR = 0.740 [0.531-1.032]; p = 0.091), homozygous recessive (G/G vs. C/C + G/C) (odds ratio [OR] = 01.432 [0.930-2.206]; p = 0.126), heterozygous (G/C vs. C/C + G/G) (OR = 1.084 [0.786-1.494]; p = 0.682), and additive (OR 0.778 [0.617-0.981]; p = 0.039) models. Similarly, the GT genotype in the rs185070757 (T/G) miR-196a2 variant did not differ between cases and controls with any models (p > 0.05). For the first time, we report no association of miR-146a rs2910164 (G/C) and miR-196a2 rs185070757 (T/G) with RA in a Pakistani population. A subsequent bioinformatic analysis revealed that the CC genotype of miR-146a rs2910164 might have a protective role against RA pathogenesis, with no effect observed with the miR-196a2 rs185070757.Conclusion: Our findings suggest that these miRNAs might have little-to-no impact on the RA pathogenesis in the Pakistani population.