外周血单个核细胞中mRNA表达与类风湿关节炎活动度的相关性研究

目的 以28个关节疾病活动度评分(disease activity score in 28 joints,DAS28)为基础对不同活动度群组的类风湿关节炎(rheumatoid arthritis, RA)病人和健康人群进行分析,挑选出RA活动度相关基因,为RA的诊断治疗提供新思路与线索。方法 收集苏州大学附属第一医院风湿免疫科门诊28个不同活动度的RA病人和18个健康人的基本信息并对它们外周血单个核细胞中mRNA水平进行检测,通过生物信息学分析寻找活动度相关基因。结果 筛选出80个单纯与RA活动度相关的基因,36个与RA活动度和发病都有关系的基因。在这些基因中,12个单纯与活动度相关的基因(SOCS3、C12orf44、KIFC1、MRPS18A、GYG1、RAB35、B4GALT5、LRRC41、LILRB4、LILRA5、CR1、PDIA6)与DAS28显著相关(r值分别为0.55、0.53、0.52、0.49、0.44、0.42、0.42、0.41、0.41、0.41、0.40、0.39,P值均<0.05)且呈趋势性下降,与发病和活动度都与相关基因PPIH与DAS28显著相关(r=-0.38,P<0.05)且呈趋势性上升。生物功能聚类发现有四项功能和甲基化相关,一项功能和应激反应相关。蛋白质关联分析显示HIST1H3E、HIST1H4I、HIST1H4F、HIST1H3D和HIST1H3F这五个基因不仅出现在与甲基化相关的功能中,而且在实验、文本挖掘和共表达三个方面都存在相互关系。结论 以DAS28为基础挑选出80个单纯与RA活动度相关的基因,功能分析表明他们大多受到甲基化调控作用,部分与免疫应激反应有关。

The relationship between RNA expression and disease activity in rheumatoid arthritis in peripheral blood mononuclear cells

Objective To analyze mRNA among different rheumatoid arthritis(RA)activity groups based on disease activity score in 28 joints(DAS28),and to explore rheumatoid arthritis activity related genes.Methods Total of 28 RA patients with different activity and 18 healthy people were collected from the Outpatient Department of Rheumatology and Immunology,the First Affiliated Hospital of Suzhou University,and the expression level of mRNA in their peripheral blood mononuclear cells was detected.We also performed an enrichment analysis and protein-protein interaction to search and discuss genes related with RA activity.Results The 80 genes only related to RA activity and 36 genes both related to RA activity and disease were selected.Total of 12 genes only disease activity related,including SOCS3,C12orf44,KIFC1,MRPS18A,GYG1,RAB35,B4GALT5,LRRC41,LILRB4,LILRA5,CR1,PDIA6,which had significant correlations with DAS28(r values were 0.55,0.53,0.52,0.49,0.44,0.42,0.42,0.41,0.41,0.41,0.40 and 0.39,all P values<0.05)with a decline trend.Gene PPIH is pathogenesis and disease activity related genes,and was significantly correlated with DAS28 with a upward trend(r=-0.38,P<0.05).Enrichment analysis found four functions related to methylation and one function related to stress response.Protein association analysis showed that the five genes,HIST1H3D,HIST1H3E,HIST1H3F,HIST1H4F and HIST1H4I,not only appeared in the function related to methylation,but also have mutual relationship in experiment,text mining and co-expression.Conclusions The 80 genes related to RA activity were selected based on DAS28.Functional analysis showed that most of genes were regulated by methylation,and some of them were related to immune stress.