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.
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 SLEpatients 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 SLEpatients. 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:SLEpatients 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 SLEpatients 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 SLEpatients 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.
Authors: Carlos G Penaloza; Brian Estevez; Dinah M Han; Melissa Norouzi; Richard A Lockshin; Zahra Zakeri Journal: FASEB J Date: 2013-10-25 Impact factor: 5.191
Authors: Paul Renauer; Patrick Coit; Matlock A Jeffries; Joan T Merrill; W Joseph McCune; Kathleen Maksimowicz-McKinnon; Amr H Sawalha Journal: Lupus Sci Med Date: 2015-09-15