Research Center of Gout and Hyperuricemia, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China.
Department of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China.
Curr Rheumatol Rev. 2023 Jun 5;19(3):336-344. doi: 10.2174/1573397119666230214104242.
MicroRNA-146a (miR-146a) plays a critical role in the regulation of autoinflammatory diseases, including gout. There is growing evidence that miR-146a gene single nucleotide polymorphisms (SNPs) are associated with different diseases, but no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now.
The purpose of this study was to examine the relationship between the miR-146a rs57095329 genetic polymorphism and the susceptibility to primary gout in the Chinese Han population.
A case-control study was performed in this report to examine the potential association between gout and the functional rs57095329 SNP of miR-146a in a Chinese population consisting of 448 primary gout patients (containing 76 tophi patients) and 418 healthy controls. MiR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured in 81 gout patients (including 32 tophi patients and 49 non-tophi patients) and 47 healthy subjects.
There was no significant difference found in the distribution of miR-146a rs57095329 between 448 gout patients and 418 healthy subjects (P > 0.05). However, significant differences in genotypes and allele distributions were found between 76 gout with tophi patients and 418 healthy subjects, as well as between gout with tophi (76) and with no tophi patients (372) (P < 0.01, respectively). Gout patients with AG/GG genotypes had a 0.323-fold reduced risk for tophi than those with the AA genotype, and the G allele had a 0.362-fold reduced risk of tophi. Furthermore, in 32 tophi patients, the GG genotype was significantly associated with increased expression of miR- 146a.
Our findings suggest that rs57095329 may play a protective role in tophi gout susceptibility, and rs57095329 A > G variant may modulate the expression of miR-146a in tophi patients.
微小 RNA-146a（miR-146a）在自身炎症性疾病（包括痛风）的调控中发挥着关键作用。越来越多的证据表明，miR-146a 基因单核苷酸多态性（SNP）与不同疾病相关，但目前尚未有关于 miR-146a 基因多态性与痛风相关性的遗传相关性研究。
本研究旨在探讨 miR-146a rs57095329 基因多态性与中国汉族人群原发性痛风易感性的关系。
本研究采用病例对照研究，共纳入 448 例原发性痛风患者（包括 76 例痛风石患者）和 418 例健康对照者，分析 miR-146a rs57095329 与痛风的潜在相关性。在 81 例痛风患者（包括 32 例痛风石患者和 49 例非痛风石患者）和 47 例健康对照者中检测外周血单个核细胞（PBMCs）中 miR-146a 的表达。
miR-146a rs57095329 在 448 例痛风患者和 418 例健康对照者中的分布无显著性差异（P>0.05）。然而，在 76 例痛风合并痛风石患者和 418 例健康对照者之间，以及在痛风合并痛风石（76 例）和无痛风石患者（372 例）之间，miR-146a rs57095329 的基因型和等位基因分布存在显著性差异（均 P<0.01）。与 AA 基因型相比，AG/GG 基因型的痛风患者发生痛风石的风险降低了 0.323 倍，G 等位基因发生痛风石的风险降低了 0.362 倍。此外，在 32 例痛风石患者中，GG 基因型与 miR-146a 的表达增加显著相关。
本研究结果提示，rs57095329 可能在痛风石性痛风易感性中起保护作用，rs57095329A>G 变异可能调节痛风石患者 miR-146a 的表达。
