Genome-wide DNA methylation analysis in Graves' disease

Abstract

As an autoimmune disease, Graves' disease (GD) is associated with many genetic and environmental risk factors. Although the exact mechanism remains unclear, epigenetic determinants, such as DNA methylation, are thought to contribute to the pathogenesis of GD. Here, we for the first time reported the DNA methylation pattern in GD through a high-throughput analysis. In order to investigate genome-wide DNA methylation profile of GD, methyl-DNA immunoprecipitation (MeDIP) and Nimblegen human DNA methylation 3 × 720 K promoter plus CpG island microarrays were used to identify differentially methylated regions (DMRs) from blood samples in GD patients. Quantitative methylation-specific PCR (qMSP) was used to validate the methylation state of candidate genes. Transcription level of each gene was estimated by quantitative real-time PCR (qRT-PCR). A total of 132 hypermethylated and 133 hypomethylated regions were identified in GD. The methylation of ICAM1 in GD patients and normal controls was significantly different (p<0.05). In the female group, significantly decreased methylation was observed in GD patients compared with normal controls (p<0.05). The transcription of ICAM1 at the mRNA level was significantly higher in GD patients compared with normal controls (p<0.05). Besides, the transcription of DNMT1 and MECP2 at the mRNA level was significantly decreased in GD patients compared with normal controls (p<0.05). Our findings revealed that the DNA methylation pattern in GD was distinct from that of controls. These results provided new molecular insights into the pathogenesis of GD.

Keywords: DNA methylation; DNMTs; Graves' disease; ICAM1; MBDs; MeDIP-chip.