Global DNA methylation, DNMT1, and MBD2 in patients with systemic lupus erythematosus

Abstract

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 systemic lupus erythematosus (SLE), 108 patients with SLE and 97 healthy controls were enrolled in this study. DNA and total RNA were extracted from the peripheral blood mononuclear cells of the SLE patients and the controls. The global methylation levels of DNA were measured in 63 patients with SLE and 68 healthy controls by the ELISA method. DNMT1 and MBD2 mRNA were also detected in 108 SLE patients and 97 controls using the quantitative real-time polymerase chain reaction method. The global methylation level of DNA was significantly decreased in the SLE patients in comparison with that in the controls (p < 0.001, 95% CI = 0.1573-0.5052). The patients with SLE have higher expressions of DNMT1 and MBD2 mRNA than the controls (p < 0.001, 95% CI = -0.0049 - -0.0019 and p = 0.001, 95% CI = -0.0119 - -0.0029, respectively). We also found that there were no significant differences in the methylation level and the expression of DNMT1 and MBD2 mRNA between the active and the inactive SLE patients. A positive correlation was also found between DNMT1 and MBD2 mRNA expressions in the SLE patients (p < 0.001). This study demonstrated that the patients with SLE had a significantly lower level of DNA methylation than the controls. The expression of both DNMT1 and MBD2 mRNA was significantly increased in the SLE patients compared with the controls. This study also showed a positive correlation between DNMT1 and MBD2 mRNA levels in the patients with SLE.

Gene-gene and gene-sex epistatic interactions of <i>DNMT1</i>, <i>DNMT3A</i> and <i>DNMT3B</i> in autoimmune thyroid disease

“…Besides inducing transcriptional silencing, DNMT3A plays an important role in immunoregulation, a dynamic regulation of both adaptive and innate immune mechanisms [5,6]. Recent studies have found aberrant DNA methylation patterns and expressions of DNMTs in autoimmune diseases, such as systemic lupus erythematosus (SLE) [7] and rheumatoid arthritis (RA) [8,9]. Polymorphism studies have also indicated that DNMTs function as genetic risk factors for autoimmune diseases.…”

Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women

“…6,7 There is also evidence that altered DNA methylation patterns are associated with other pathologies such as autoimmune and cardiovascular diseases. [7][8][9] DNa methylation is an epigenetic modification essential for the regulation of gene expression that has been implicated in many diseases, including cancer. Few studies have investigated the wide range of potential predictors of global DNa methylation, including biomarkers.…”

Mbd2 Promotes Foxp3 Demethylation and T-Regulatory-Cell Function

“…Surprisingly, it has been proposed that one well-characterized 44-kDa Mbd protein, Mbd2, may act as a DNA demethylase by removing repressive methyl residues and thereby activating gene transcription (4). Overexpression of Mbd2 can activate gene expression as a result of demethylation of CpG islands within promoter regions (5), and correlations between high levels of Mbd2 and DNA demethylation were reported in several autoimmune diseases, including systemic lupus erythematosus (SLE), dermatomyositis and systemic sclerosis (6)(7)(8), rheumatoid arthritis (9), and psoriasis (10), as well as in breast cancer (11). However, other groups have failed to detect any demethylation activity of Mbd2 (12)(13)(14), and so it remains controversial as to whether Mbd2 itself has direct demethylase activity.…”