Abstract
Myasthenia gravis (MG) is a common neuromuscular junction disorder and autoimmune disease mediated by several antibodies. Several studies have shown that genetic factors play an important role in MG pathogenesis. To gain insight into the epigenetic factors affecting MG, we report here genome-scale DNA methylation profiles of MG. DNA was extracted from eight MG patients and four healthy controls for genome-wide DNA methylation analysis using the Illumina HumanMethylation 850K BeadChip. Verification of pyrosequencing was conducted based on differential methylation positions. Subsequently, C2C12 and HT22 cell lines (derived from mouse) were treated with demethylation drugs. Transcribed mRNA of the screened differential genes was detected using quantitative real-time PCR. The control and MG group were compared, and two key probe positions were selected. The corresponding genes were CAMK1D and CREB5 (P < 0.05). Similarly, the myasthenic crisis (MC) and non-MC group were compared and four key probe positions were selected. The corresponding genes were SAV1, STK3, YAP1, and WWTR1 (P < 0.05). Subsequently, pyrosequencing was performed for verification, revealing that hypomethylation of CAMK1D was significantly different between the MG and control group (P < 0.001). Moreover, transcription of CREB5, PKD, YAP1, and STK3 genes in the C2C12 cells was downregulated (P < 0.05) after drug treatment, but only YAP1 mRNA was downregulated in HT22 cells (P < 0.05). This is the first study to investigate genome-scale DNA methylation profiles of MG using 850 K BeadChip. The identified molecular markers of methylation may aid in the prevention, diagnosis, treatment, and prognosis of MG.