北京大学学报(医学版) ›› 2021, Vol. 53 ›› Issue (6): 1020-1025. doi: 10.19723/j.issn.1671-167X.2021.06.002
LOU Xue,LIAO Li,LI Xing-jun,WANG Nan,LIU Shuang,CUI Ruo-mei,XU Jian()
摘要:
目的:通过检测外周血肿瘤坏死因子样凋亡弱诱导剂(tumor necrosis factor-like weak inducer of apoptosis,TWEAK)基因DNA甲基化水平、mRNA表达水平及血清蛋白浓度,探究TWEAK基因与类风湿关节炎(rheumatoid arthritis,RA)发病机制的关联。方法:采用MassARRAY法检测112例RA患者和86例匹配的健康志愿者外周血TWEAK基因DNA甲基化水平,采用实时荧光定量PCR法检测外周血TWEAK基因mRNA表达水平,采用酶联免疫吸附测定法检测血清TWEAK蛋白浓度。比较RA组和健康对照组TWEAK基因DNA甲基化水平、mRNA表达水平及血清蛋白浓度,并分析其与疾病活动度的关系。结果:RA组TWEAK基因总体甲基化水平和CpG_11、CpG_17.18.19.20、CpG_40.41.42位点甲基化水平高于健康对照组(P=0.002,P=0.01,P=0.006,P=0.002),高疾病活动度组CpG_55.56位点甲基化水平高于中低疾病活动度组(P=0.041)。RA组外周血TWEAK基因mRNA表达水平低于健康对照组(P=0.023),高疾病活动度组TWEAK基因mRNA表达水平低于中低疾病活动度组(P=0.035)。RA组血清TWEAK蛋白浓度与健康对照组差异无统计学意义(P=0.508), 但其与mRNA表达水平呈正相关(r=0.482,P<0.001)。结论:TWEAK基因与RA的发病和病情活动程度密切相关,其高甲基化状态可能为调控mRNA低表达的表观遗传学机制之一,可作为临床监测和评价RA病情的重要指标之一。
中图分类号:
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