associations between the expression of epigenetically regulated genes and the expression of dnmts and mbds in systemic lupus erythematosus之间的关联epigenetically调节基因的表达和表达dnmts mbds系统性红斑狼疮.pdfVIP

Associations between the Expression of Epigenetically Regulated Genes and the Expression of DNMTs and MBDs in Systemic Lupus Erythematosus ´ ´ ´ Eva Balada*, Jesus Castro-Marrero, Lledo Felip, Josep Ordi-Ros, Miquel Vilardell-Tarres ´ Research Unit in Systemic Autoimmune Diseases, Vall d’Hebron Research Institute, Hospital Vall d’Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain Abstract Objectives: We determined the expression of ITGAL, PRF1, KIR2DL4, CD70, and CD40LG in patients with SLE and performed correlations with the global DNA methylation status and the levels of three DNA methylation enzymes and two methyl CpG- binding domain (MBD) proteins. Patients and Methods: CD4+ T cells were isolated from 35 SLE patients and 30 healthy controls. DNA deoxymethylcytosine content was measured by an enzyme-linked immunosorbent assay (ELISA). Transcript levels of ITGAL, PRF1, KIR2DL4, CD70, CD40LG, DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4 were quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR). Results: SLE patients had significantly elevated transcript levels of ITGAL (18.61622.17 vs. 7.3369.17, p = 0.042), PRF1 (21.67626.34 vs. 10.67611.65, p = 0.039), and CD70 (1.4561.63 vs. 0.6760.28, p = 0.011). A positive correlation was observed between transcript levels of CD40LG and ITGAL (r = 0.477, p = 0.004) as well as between CD40LG and PRF1 (r = 0.557, p = 0.001). Transcript levels of KIR2DL4 were higher than controls’ but it did not reach statistical significance (1.3663.52 vs. 0.2260.79, p = 0.560). A tight relationship with gl