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系统性红斑狼疮患者的全球 DNA 甲基化、DNMT1 和 MBD2。

Global DNA methylation, DNMT1, and MBD2 in patients with systemic lupus erythematosus.

机构信息

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.

出版信息

Lupus. 2011 Feb;20(2):131-6. doi: 10.1177/0961203310381517. Epub 2010 Nov 15.

DOI:10.1177/0961203310381517
PMID:21078759
Abstract

To investigate the associations of DNA methylation levels and mRNA expressions of DNA cytosine-5-methyltransferase 1 (DNMT1) and methyl CpG-binding domain 2 (MBD2) with systemic lupus erythematosus (SLE), 108 patients with SLE and 97 healthy controls were enrolled in this study. DNA and total RNA were extracted from the peripheral blood mononuclear cells of the SLE patients and the controls. The global methylation levels of DNA were measured in 63 patients with SLE and 68 healthy controls by the ELISA method. DNMT1 and MBD2 mRNA were also detected in 108 SLE patients and 97 controls using the quantitative real-time polymerase chain reaction method. The global methylation level of DNA was significantly decreased in the SLE patients in comparison with that in the controls (p < 0.001, 95% CI = 0.1573-0.5052). The patients with SLE have higher expressions of DNMT1 and MBD2 mRNA than the controls (p < 0.001, 95% CI = -0.0049 - -0.0019 and p = 0.001, 95% CI = -0.0119 - -0.0029, respectively). We also found that there were no significant differences in the methylation level and the expression of DNMT1 and MBD2 mRNA between the active and the inactive SLE patients. A positive correlation was also found between DNMT1 and MBD2 mRNA expressions in the SLE patients (p < 0.001). This study demonstrated that the patients with SLE had a significantly lower level of DNA methylation than the controls. The expression of both DNMT1 and MBD2 mRNA was significantly increased in the SLE patients compared with the controls. This study also showed a positive correlation between DNMT1 and MBD2 mRNA levels in the patients with SLE.

摘要

为了研究 DNA 胞嘧啶-5-甲基转移酶 1(DNMT1)和甲基 CpG 结合域 2(MBD2)的 DNA 甲基化水平和 mRNA 表达与系统性红斑狼疮(SLE)之间的关系,本研究纳入了 108 例 SLE 患者和 97 名健康对照者。从 SLE 患者和对照者的外周血单核细胞中提取 DNA 和总 RNA。采用 ELISA 法检测 63 例 SLE 患者和 68 名健康对照者的 DNA 整体甲基化水平。采用实时定量聚合酶链反应法检测 108 例 SLE 患者和 97 例对照者的 DNMT1 和 MBD2mRNA。与对照组相比,SLE 患者的 DNA 整体甲基化水平显著降低(p<0.001,95%CI=0.1573-0.5052)。SLE 患者的 DNMT1 和 MBD2 mRNA 表达均高于对照组(p<0.001,95%CI=-0.0049--0.0019 和 p=0.001,95%CI=-0.0119--0.0029)。我们还发现,活动期和非活动期 SLE 患者的 DNA 甲基化水平和 DNMT1 和 MBD2 mRNA 表达无显著差异。SLE 患者的 DNMT1 和 MBD2 mRNA 表达之间也存在正相关(p<0.001)。本研究表明,SLE 患者的 DNA 甲基化水平明显低于对照组。SLE 患者的 DNMT1 和 MBD2 mRNA 表达均明显高于对照组。本研究还显示 SLE 患者的 DNMT1 和 MBD2 mRNA 水平之间存在正相关。

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