Hypermethylation of glucocorticoid receptor gene promoter results in glucocorticoid receptor gene low expression in peripheral blood mononuclear cells of patients with systemic lupus erythematosus

摘要

Our aim was to investigate the relationship between the DNA methylation status of glucocorticoid receptor (GR) gene promoter and mRNA expression level of GR alpha gene of peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE). Fifteen newly emerging SLE patients and fifteen healthy controls were enrolled in this study. DNA and total RNA were extracted from the PBMCs of the SLE patients and healthy controls. The DNA methylation status of GR gene promoter 1 of PBMCs was detected through bisulfite-sequencing PCR. The mRNA expression of GR alpha, DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and growth arrest, and DNA damage-induced 45 alpha (GADD45 alpha) of PBMCs was detected using the quantitative real-time polymerase chain reaction method. The mRNA expression of GR alpha was significantly declined in SLE patients, and the mRNA expression of DNMT1 and GADD45 alpha was significantly elevated in SLE patients. The global methylation status of PBMCs in SLE patients was obviously lower than healthy controls. There were 38, 25, 30, and 49 CpG islands in amplified fragment of GR promoter 1D, 1E, 1F, and 1H, respectively. The overall mean methylation status of the 152 CpG islands of the four promoters was significantly elevated in SLE patients. There was a negative correlation between hypermethylation of GR promoter and GR alpha mRNA expression in SLE patients. This study demonstrated that hypermethylation of GR alpha promoter may result in GR alpha gene low expression in PBMCs of patients with SLE. This study also found that the global methylation status of PBMCs in SLE patients was obviously lower than healthy controls, and it was related to the elevated GADD45 alpha mRNA expression in SLE patients. These conclusions have to be certified by larger-scale clinical studies.