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Single nucleotide polymorphisms in the Dicer gene modify the risk of systemic lupus erythematosus
European Journal of Inflammation ( IF 0.7 ) Pub Date : 2024-03-28 , DOI: 10.1177/1721727x241243340
Jingjing Zhang 1 , Yufei Zhao 1 , Song Wang 1 , Shasha Zhang 1 , Xiaoyun Zhang 1 , Chenxing Peng 2 , Qingyi Liu 3
Affiliation  

ObjectiveMicroRNA-related single-nucleotide polymorphisms (miR-SNPs) can alter microRNA (miRNA) expression profiles, thereby influencing the risk of rheumatic diseases. Herrin a case control study, six miR-SNPs in miRNA processing machinery genes, namely RAN (rs14035), XPO5 (rs11077), Dicer (rs3742330), GEMIN3 (rs197412), GEMIN4 (rs2740348), and TNRC6B (rs9623117), were genotyped to assess their correlation with the risk of systemic lupus erythematosus (SLE).MethodsWe included 119 patients with SLE and 130 healthy controls. The genotypes of the six miR-SNPs were determined using polymerase chain reaction (PCR). Serum cytokine levels were assessed using a cytometric bead array, and fluorescent probe technology was used to determine plasma reactive oxygen species (ROS) levels.ResultsThe AA genotype of Dicer was correlated with a 0.566-fold decreased risk of SLE compared with that of the AG + GG genotype (odds ratio, 0.566; 95% CI, 0.342–0.935; p = .026), and the rs3742330 A allele was associated with a significantly decreased risk of SLE ( p = .035) compared with that of the rs3742330G allele. Additionally, AA genotype carriers exhibited lower levels of interleukin-6 (IL-6) in the blood ( p = .013). Subsequent analysis revealed increased ROS production in patients with SLE than that in the controls (621.042 ± 425.285 vs 499.966 ± 302.273, p = .011).ConclusionOur findings suggest that ROS generation participates in SLE pathogenesis. The identification of Dicer gene SNP rs3742330 as a potential modifier of SLE risk via mediating IL-6 overproduction suggests a potential avenue for targeted interventions to manage SLE and its associated immune dysregulation.

中文翻译:

Dicer 基因中的单核苷酸多态性改变系统性红斑狼疮的风险

目的MicroRNA相关的单核苷酸多态性(miR-SNP)可以改变microRNA(miRNA)的表达谱,从而影响风湿性疾病的风险。 Herrin 的一项病例对照研究,对 miRNA 加工机器基因中的 6 个 miR-SNP,即 RAN (rs14035)、XPO5 (rs11077)、Dicer (rs3742330)、GEMIN3 (rs197412)、GEMIN4 (rs2740348) 和 TNRC6B (rs9623117) 进行了基因分型评估它们与系统性红斑狼疮 (SLE) 风险的相关性。方法我们纳入了 119 名 SLE 患者和 130 名健康对照者。使用聚合酶链式反应 (PCR) 确定了 6 个 miR-SNP 的基因型。使用细胞计数珠阵列评估血清细胞因子水平,并使用荧光探针技术测定血浆活性氧(ROS)水平。结果与 AG 相比,Dicer 的 AA 基因型与 SLE 风险降低 0.566 倍相关+ GG 基因型(比值比,0.566;95% CI,0.342–0.935;p = .026),与 rs3742330G 等位基因相比,rs3742330 A 等位基因与 SLE 风险显着降低相关(p = .035) 。此外,AA 基因型携带者血液中白细胞介素 6 (IL-6) 水平较低 (p = .013)。随后的分析显示,SLE 患者的 ROS 生成量高于对照组(621.042 ± 425.285 vs 499.966 ± 302.273,p = .011)。结论我们的研究结果表明,ROS 生成参与 SLE 发病机制。 Dicer 基因 SNP rs3742330 的鉴定通过介导 IL-6 过量产生作为 SLE 风险的潜在修饰因子,表明有针对性的干预措施管理 SLE 及其相关免疫失调的潜在途径。
更新日期:2024-03-28
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