Global DNA methylation, DNMT1, and MBD2 in patients with rheumatoid arthritis.

Objectives: To investigate the associations of DNA methylation levels and mRNA expressions of DNA cytosine-5-methyltransferase 1 (DNMT1) and methyl CpG-binding domain 2 (MBD2) with rheumatoid arthritis (RA).

Methods: The global methylation status of DNA was measured in 65 patients with RA and 64 healthy controls by the ELISA method. DNMT1 and MBD2 mRNA were also detected in 177 RA patients and 95 controls using the quantitative real-time polymerase chain reaction method.

Results: The global methylation of DNA was significantly decreased in the RA patients compared to the controls (p=0.005, 95% CI=0.0835-0.4503). The patients with RA had higher expressions of DNMT1 and MBD2 mRNA than the controls (p<0.001, 95% CI=-0.0024 to -0.0053 and p<0.001, 95% CI=-0.0079 to -0.0167, respectively). We also found that the MBD2 mRNA level was not related to the disease activity of RA. However, the expression of DNMT1 mRNA tended to be associated with the disease activity of RA (p=0.08). The levels of DNA methylation and DNMT1 mRNA were significantly decreased in the patients with anti-CCP antibody compared with those without (p=0.005, 95% CI=-0.7333 to -0.1373 and p=0.003, 95% CI=-0.0071 to -0.0022, respectively). The differences in the methylation level and expressions of DNMT1 and MBD2 were not significant between the patients treated with and without anti-TNFα biological agents (Enbrel or Humira).

Conclusion: This study demonstrated that the RA patients have a significantly lower level of DNA methylation than the controls. Moreover, RA patients have higher expressions of DNMT1 and MBD2 mRNA. The anti-TNFα biological agents do not seem to affect DNA methylation and mRNA expressions of DNMT1 and MBD2 in RA patients.