title: Associations between aberrant DNA methylation and transcript levels of DNMT1 and MBD2 in CD4+T cells from patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Qin
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Yang
authors.forename: Shang-Shang
authors.initials: SS
authors.lastname: Wang
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Shi
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C489325:MBD2 protein, human; D012333:RNA, Messenger; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human