The Effect of Estrogen on the DNA Methylation of B Cells in Patients with SLE / 대한류마티스학회지

ABSTRACT

OBJECTIVE: Epigenetics is an important, alternative mechanism of gene regulation that is independent of the nucleotide sequences of DNA. We investigated mRNA levels for DNA methyltransferase-1 (DNMT-1), and the effect of estrogen on the expression of DNMT-1 level in T cells and B cells from patients with systemic lupus erythematosus (SLE) and healthy subjects, and assessed the possible etiological role of DNA methylation in the pathogenesis of SLE. METHODS: mRNA levels for DNMT-1 in CD4+ T cells and CD19+ B cells from 37 patients with SLE and 12 healthy controls were examined using RT-PCR. We used specific primer for DNMT-1 and beta actin, The effect of estrogen on the DNA methylation was measured by the mRNA level of DNMT-1 CD4+ T cells and CD19+ B cells treated with 100 nM of 17beta-estradiol for 72 hour. RESULTS: The levels of DNMT-1 mRNA were significantly lower in CD4+ T cells and CD19+ B cells from SLE patients compared with healthy controls. We observed the suppression of the levels of DNMT-1 mRNA by stimulated with estrogen in patients with SLE patients, especially in CD19+B cells. DNA hypomethylation of B cells was tend to be correlated with the level of anti-ds DNA antibody without statistical significance (r=-0.43, p=0.3). CONCLUSION: Our observations suggest that suppression of DNMT-1 by estrogen in B cells from patients with SLE might be related to the pathogenesis of SLE. Epigenetic studies may provide clues for developing new treatment strategies of SLE.