a Department of Rheumatology and Immunology , the First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , China.
b Wuxi Center for Disease Control and Prevention , Wuxi , Jiangsu , China.
Autoimmunity. 2019 Feb;52(1):21-26. doi: 10.1080/08916934.2019.1581773. Epub 2019 Mar 1.
Recent evidence has demonstrated that UBASH3A play a pivotal role in multiple autoimmune diseases. In this study, we explored the association between UBASH3A gene single-nucleotide polymorphisms (SNPs) and rheumatoid arthritis (RA) in a Chinese Han population. We also comparatively evaluated the UBASH3A expression profile in peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls.
Four UBASH3A polymorphisms (rs1893592, rs11203203, rs2277798, and rs3788013) were studied in 553 patients with RA and 587 controls in a Chinese population. Genotyping was performed using the Fluidigm 192.24 Dynamic Array Integrated Fluidic Circuit (IFC). For gene expression study, UBASH3A mRNA levels of 30 RA patients and 31 healthy individuals were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Data were analyzed by SPSS 19.0 software.
A significant association between rs1893592 polymorphism and RA was found under all genetic models (all p<.05). We also discovered a significant association between rs3788013 polymorphism and RA in the allele and genotype distributions, as well as the recessive model (all p<.05). Moreover, we found the genotype distribution and allele frequency of rs1893592 were significantly associated with RF phenotype in the RA patients (χ = 6.786, p=.034; χ = 4.534, p=.033; respectively). We also found the genotype distribution and allele frequency of rs2277798 were significantly associated with anti-CCP phenotype in the RA patients (χ = 7.873, p=.020; χ = 4.473, p=.034; respectively). However, we did not detect any significant associations between rs11203203 and RA susceptibility and autoantibody profiles (all p>.05). The mRNA expression of UBASH3A was increased in PBMCs of patients with RA when compared to healthy controls (p=.001).
Our observations suggested that the dysregulation of UBASH3A might be associated with the pathogenesis of RA, and UBASH3A gene polymorphisms (rs1893592 and rs3788013) might contribute to RA susceptibility in Chinese Han population.
最近的证据表明，UBASH3A 在多种自身免疫性疾病中发挥着关键作用。在这项研究中，我们探讨了中国汉族人群中 UBASH3A 基因单核苷酸多态性（SNP）与类风湿关节炎（RA）之间的关联。我们还比较评估了 RA 患者和健康对照者外周血单个核细胞（PBMC）中 UBASH3A 的表达谱。
在中国人群中，对 553 例 RA 患者和 587 例对照进行了 4 个 UBASH3A 多态性（rs1893592、rs11203203、rs2277798 和 rs3788013）的研究。采用 Fluidigm 192.24 动态阵列集成流体回路（IFC）进行基因分型。采用实时定量聚合酶链反应（RT-qPCR）评估 30 例 RA 患者和 31 例健康个体的 UBASH3A mRNA 水平。数据分析采用 SPSS 19.0 软件。
在所有遗传模型下，rs1893592 多态性与 RA 均存在显著相关性（均 P<.05）。我们还发现 rs3788013 多态性与 RA 在等位基因和基因型分布以及隐性模型中存在显著相关性（均 P<.05）。此外，我们发现 RA 患者中 rs1893592 的基因型分布和等位基因频率与 RF 表型显著相关（χ²=6.786，P=.034；χ²=4.534，P=.033）。我们还发现 RA 患者中 rs2277798 的基因型分布和等位基因频率与抗 CCP 表型显著相关（χ²=7.873，P=.020；χ²=4.473，P=.034）。然而，我们没有发现 rs11203203 与 RA 易感性和自身抗体谱之间存在任何显著关联（均 P>.05）。与健康对照组相比，RA 患者 PBMC 中 UBASH3A 的 mRNA 表达增加（P=.001）。
我们的观察结果表明，UBASH3A 的失调可能与 RA 的发病机制有关，UBASH3A 基因多态性（rs1893592 和 rs3788013）可能导致中国汉族人群易患 RA。
