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 (χ2 = 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.

中文翻译：

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探索巴基斯坦人群中 miR-146a/rs2910164 和 miR-196a2/rs185070757 与类风湿关节炎的关联和分子影响。

引言 MicroRNA (miRNA) 是一类参与基因表达转录后调控的新型分子，因此据报道在类风湿性关节炎 (RA) 的发病机制中发挥着至关重要的作用。我们的目的是研究 miR-146a rs2910164 (G/C) 和 miR-196a2 rs185070757 (T/G) 与巴基斯坦患者 RA 易感性的关系，并以生物信息学方式预测这些 miRNA 的分子功能。方法 对 600 名个体进行病例对照研究，其中包括 300 名 RA 患者和 300 名匹配的健康对照。通过难治性突变系统-聚合酶链式反应的四引物扩增进行基因分型，并使用不同的模型统计确定变异与RA之间的关联。结果 对于 miR-146a 中的变异 rs2910164 (G/C)，使用共显性 (χ2 = 4.33；p = 0.114)、纯合显性 (C/C) 确定，RA 病例和对照之间的基因型分布没有差异。与 G/G + C/G) (OR = 0.740 [0.531-1.032]; p = 0.091)，纯合隐性（G/G 与 C/C + G/C）（比值比 [OR] = 01.432 [ 0.930-2.206]；p = 0.126）、杂合（G/C 与 C/C + G/G）（OR = 1.084 [0.786-1.494]；p = 0.682）和加性（OR 0.778 [0.617-0.981] ；p = 0.039) 模型。同样，rs185070757 (T/G) miR-196a2 变体中的 GT 基因型在任何模型的病例和对照之间没有差异 (p > 0.05)。我们首次报告 miR-146a rs2910164 (G/C) 和 miR-196a2 rs185070757 (T/G) 与巴基斯坦人群中的 RA 没有关联。随后的生物信息学分析表明，miR-146a rs2910164 的 CC 基因型可能对 RA 发病机制具有保护作用，而 miR-196a2 rs185070757 没有观察到任何作用。结论 我们的研究结果表明，这些 miRNA 可能对巴基斯坦人群的 RA 发病机制几乎没有影响。