Analysis of associations between the patterns of global DNA hypomethylation and expression of DNA methyltransferase in patients with systemic lupus erythematosus.

摘要

OBJECTIVES: To analyze associations between the patterns of global DNA hypomethylation and expression of DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) in patients with systemic lupus erythematosus (SLE) and to obtain a deeper understanding of the role that epigenetic mechanism may have on SLE. METHODS: The global DNA methylation profile in T cells from 34 patients with SLE and 23 healthy controls was assessed by the specific monoclonal antibodies to 5-methylcytosine and was analyzed quantitatively by flow cytometry. Real-time reverse transcription-polymerase chain reaction was applied to analyze DNMTs (DNMT1, DNMT3A, and DNMT3B) mRNA levels in T cells from patients and controls. RESULTS: Patients with SLE had significantly global DNA hypomethylation than that in controls (P = 0.004), and the global DNA methylation was inverse correlated with the SLE Disease Activity Index (P < 0.0005). Patients with SLE had significantly lower levels of DNMT1 mRNA than that in controls (P < 0.0005), and there was no correlation between the level of DNMT1 mRNA and SLE Disease Activity Index, neither the correlation between the levels of DNMT1 mRNA and global DNA methylation. There was no statistical difference in levels of DNMT3A mRNA between the patients with SLE and normal controls. The levels of DNMT3B mRNA were very low, and there was no difference in patients with SLE and normal controls. CONCLUSIONS: Global DNA hypomethylation plays an important role in the pathogenesis of SLE. Lower expression of DNMT1 mRNA may play a role in the pathogenesis of SLE, which is not the exclusive regulation factor of global DNA methylation of SLE. The mechanism of global DNA hypomethylation in patients with SLE was complicated. Enzymes that participate in DNA methylation and demethylation events should be studied further.