The circulating methylation level of GRB2 is Associated with the progression of rheumatoid arthritis

GRB2 (growth factor receptor binding protein 2) plays an important role in the immune mechanism of various diseases such as tumor and osteosarcoma. However, there are few studies on RA at present, and data mining has found that RA is a differentially expressed gene, which may become a target for the diagnosis or treatment of RA. In this study, the methylation level of cg01884715_43 located in GRB2 was analyzed by methylation targets. In patients with course20, cg01884715_43 methylation level was positively correlated with RF (R=-0.32, P=0.03).IIn patients with DAS28-CRP<2.6, cg01884715_43 methylation level was positively correlated with courses (R=0.21, P=0.02) and swollen joints (R=0.24, P=0.01)I.In patients with DAS28-ESR<2.6, cg01884715_43 methylation level was positively correlated with courses (R=0.35, P=1.83X10-3), Swollen joints (R=0.23, P=0.04) and CRP (R=0.27, P=0.02).In conclusion, the methylation level of cg01884715_43 on GRB provides evidence for the progression of RA.

生长因子受体结合蛋白2（growth factor receptor binding protein 2，GRB2）在肿瘤、骨肉瘤等多种疾病的免疫机制中发挥关键作用。但目前针对类风湿关节炎（Rheumatoid Arthritis，RA）的相关研究较为匮乏，经数据挖掘发现，RA属于差异表达基因，有望成为类风湿关节炎诊断或治疗的潜在靶点。本研究通过甲基化靶标分析，对位于GRB2基因上的cg01884715_43位点的甲基化水平展开分析。在病程为20的患者群体中，cg01884715_43的甲基化水平与类风湿因子（Rheumatoid Factor，RF）呈正相关（R=-0.32，P=0.03）。在基于C反应蛋白的28关节疾病活动度评分（DAS28-CRP）<2.6的患者中，cg01884715_43的甲基化水平与病程（R=0.21，P=0.02）及肿胀关节数（R=0.24，P=0.01）呈正相关。在基于红细胞沉降率的28关节疾病活动度评分（DAS28-ESR）<2.6的患者中，cg01884715_43的甲基化水平与病程（R=0.35，P=1.83×10^-3）、肿胀关节数（R=0.23，P=0.04）及C反应蛋白（C-reactive Protein，CRP）（R=0.27，P=0.02）呈正相关。综上，GRB2基因上cg01884715_43位点的甲基化水平可为类风湿关节炎的病情进展提供佐证依据。