类风湿关节炎患者外周血基因启动子区域的甲基化状态与表达
[Methylation status and expression of gene promoter region in peripheral blood of patients with rheumatoid arthritis].
作者信息
Lou X, Liao L, Li X J, Wang N, Liu S, Cui R M, Xu J
机构信息
Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
出版信息
Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Dec 18;53(6):1020-1025. doi: 10.19723/j.issn.1671-167X.2021.06.002.
OBJECTIVE
To explore the relationship between tumor necrosis factor like weak inducer of apoptosis () gene and the pathogenesis of rheumatoid arthritis (RA) by detecting the DNA methylation level, mRNA expression level and serum protein concentration of gene in peripheral blood.
METHODS
The MassARRAY method was used to detect the DNA methylation level of the gene in the peripheral blood of 112 RA patients and 86 matched healthy volunteers. The real-time quantitative polymerase chain reaction method was used to detect the mRNA expression level of the gene in the peripheral blood of the subjects. The enzyme-linked immunosorbent assay method was used to detect the serum TWEAK protein concentration of the subjects. The gene DNA methylation level, mRNA expression level and serum protein concentration between the RA group and the healthy control group were compared, and the relationship between it and the degree of disease activity analyzed.
RESULTS
The overall DNA methylation level of gene and the DNA methylation levels of CpG_11, CpG_17.18.19.20, CpG_40.41.42 site in the RA group were higher than those in the healthy control group (=0.002, =0.01, =0.006, =0.002, respectively). The DNA methylation level of CpG_55.56 site in the high disease activity group was higher than that in the medium and low disease activity group (=0.041). The expression level of gene mRNA in the peripheral blood of the RA group was lower than that of the healthy control group (=0.023). The expression level of gene mRNA in the high disease activity group was lower than that in the medium and low disease activity group (=0.035). The serum TWEAK protein concentration of the RA group was not significantly different from that of the healthy control group (=0.508), but it was positively correlated with the mRNA expression level (=0.482, < 0.001).
CONCLUSION
The gene is closely related to the onset and progression of RA, and its hypermethylation state may be one of the epigenetic mechanisms regulating its low mRNA expression, and it can be used as one of the important indicators for clinical monitoring and evaluation of RA.
目的
通过检测外周血中肿瘤坏死因子样凋亡微弱诱导剂（TWEAK）基因的DNA甲基化水平、mRNA表达水平及血清蛋白浓度，探讨其与类风湿关节炎（RA）发病机制的关系。
方法
采用MassARRAY方法检测112例RA患者及86例匹配的健康志愿者外周血中TWEAK基因的DNA甲基化水平。采用实时定量聚合酶链反应方法检测受试者外周血中TWEAK基因的mRNA表达水平。采用酶联免疫吸附测定法检测受试者血清TWEAK蛋白浓度。比较RA组与健康对照组之间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DNA甲基化水平及CpG_11、CpG_17、18、19、20、CpG_40、41、42位点的DNA甲基化水平均高于健康对照组（分别为P = 0.002、P = 0.01、P = 0.006、P = 0.002）。高疾病活动度组CpG_55、56位点的DNA甲基化水平高于中、低疾病活动度组（P = 0.041）。RA组外周血中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的发病及病情进展密切相关，其高甲基化状态可能是调节其mRNA低表达的表观遗传机制之一，可作为临床监测和评估RA的重要指标之一。
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