DNA methylation in systemic lupus erythematosus

Abstract

Recent studies on epigenetics, including DNA methylation and its regulatory enzymes, seem likely to contribute to elucidation of the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE), although the relationship between DNA methylation and SLE has long been the subject of investigation. To obtain a deeper understanding of the role of DNA methylation in the induction of SLE, we reviewed the relationship between DNA methylation and SLE based on findings reported in the literature and our own data. Various studies, including ours, have indicated the possible importance of DNA methylation, especially hypomethylation, in the etiology of SLE. These epigenetic studies may give us clues towards elucidation of the pathogenesis of SLE and development of new therapeutic strategies for this disease.

DNA methylation: its contribution to systemic lupus erythematosus

“…Recently, various proteins that regulate gene expression have been identified, such as DNA methyltransferases (DNMT), methyl-CpG binding protein and histone-modifying enzymes [1][2][3][4]. Methylation of DNA helps to stabilise chromatin in an inactive configuration and thus inhibits gene transcription.…”

“…Furthermore, the DNMT-1 mRNA level is significantly lower in PBMC from SLE patients than in cells from normal controls [32], although no significant association has been found between DNMT-1 polymorphism and the clinical features of SLE or the risk of developing the disease [38]. On the other hand, DNMT-2 or DNMT-3 mRNA was not detected in either SLE patients or normal individuals by our real-time quantitative polymerase chain reaction (RQ-PCR) system [4]. A previous study using the reverse transcriptase (RT)-PCR method indicated that the level of DNMT-1 mRNA was lower in the T cells of SLE patients compared with that in normal controls [17].…”

“…Recent epigenetic investigations have contributed to our understanding of the pathogenesis of various disorders, including cancer, immunodeficiency and autoimmunity. Cytosine methylation of the regulatory sequences of DNA is an epigenetic mechanism that is associated with transcriptional inactivation of genes, while hypomethylation contributes to the activation of transcription [2][3][4]. Several lines of evidence have suggested that abnormalities of DNA methylation may contribute to the development of systemic lupus erythematosus (SLE).…”

Association analyses of DNA methyltransferase-1 (DNMT1) polymorphisms with systemic lupus erythematosus

“…It had been proposed that genetic factors play a significant role in susceptibility to SLE, in determining the disease expression, and in the autoantibody profiles of individuals with SLE (Wakeland et al 2001). Recently, it was demonstrated that the pathogenesis of autoimmune diseases such as SLE might be related to DNA methylation and its regulatory enzymes (Okada et al 2002;Sekigawa et al 2003). In order to identify the association of DNMT1 polymorphisms with the risk of SLE, logistic regression analyses were performed.…”

“…Specific autoantibodies accumulate progressively in patients with SLE, even when the patients remain asymptomatic (Arbuckle et al 2003;Jacob and Viard 1992). DNA methylation and its regulatory enzymes have been suggested to be involved in pathogenesis of autoimmune diseases such as SLE (Okada et al 2002;Sekigawa et al 2003). The genetic associations with the production of five autoantibodies (anti-dsDNA, anti-Sm, anti-RNP, anti-Ro, and La Abs) were analyzed with logistic regression models whilst controlling for age, disease duration, and gender as covariates.…”