Associations between aberrant DNA methylation and transcript levels of DNMT1 and MBD2 in CD4+T cells from patients with systemic lupus erythematosus

DNA甲基化 DNMT1型 DNA甲基转移酶 甲基化 发病机制 信使核糖核酸 实时聚合酶链反应 分子生物学 DNA 甲基转移酶 免疫学 生物 医学 基因 基因表达 遗传学
作者
Haihong Qin,Xiao‐Dong Zhu,Jun Liang,Yue Yang,Shangshang Wang,Weimin Shi,Jianmin Xu
出处
期刊:Australasian Journal of Dermatology [Wiley]
卷期号:54 (2): 90-95 被引量:26
标识
DOI:10.1111/j.1440-0960.2012.00968.x
摘要

Abstract Background/Objectives It seems that global DNA hypomethylation in CD4+T cells is linked to the pathogenesis of systemic lupus erythematosus ( SLE ). However, the underlying mechanism by which SLE patients show hypomethylated DNA remains unclear. This study explored the relationship between DNA methylation patterns and expression levels of DNA methyltransferases ( DNMT1) and MBD2 in CD4+T cells of SLE patients. Methods CD4+T cells were obtained from 30 patients with SLE and 18 normal controls. The global DNA methylation levels in CD4+T cells were evaluated by the Methyflash DNA methylation quantification kit. The mRNA levels of DNMT1 and MBD2 were quantified by quantitative real‐time polymerase chain reaction. Results SLE patients had significantly lower global DNA methylation levels than controls, and the global DNA methylation was inversely correlated with the SLE disease activity index ( SLEDAI ). The mRNA levels of DNMT1 in SLE patients were significantly lower than that of controls and there was no correlation between DNMT1 mRNA levels and SLEDAI but there was a positive correlation between DNMT1 mRNA levels and global DNA methylation. The mRNA levels of MBD2 in SLE patients were significantly higher than in controls, and there was positive correlation between MBD2 mRNA levels and SLEDAI and an inverse correlation between MBD2 mRNA levels and global DNA methylation. Conclusions Global DNA hypomethylation may play a pivotal role in the pathogenesis of SLE . Abnormal expression levels of DNMT1 and MBD2 mRNA may be important causes of the global hypomethylation observed in CD4+T cells in SLE .
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