Yi Zhang, Rui Ma, Shaohong Zou, Gaiyu Tong, Gulibakeranmu Abula, Manna Hu, Qing Dai
Objective: To investigate DNA methylation and hydroxymethylation in patients with somnipathy combined with type 2 diabetes, and to explore the effects of DNA methylation and hydroxymethylation on gene expression.
Methods: Thirty patients with somnipathy combined with type 2 diabetes and 20 patients with type-2 diabetes but without somnipathy were considered. DNA methylation of Disks Large Homolog 4 (DLG4) and Ras-related protein Rab-11 (Rab11) was detected by bisulfite sequencing and DNA hydroxymethylation of activity-regulated cytoskeleton-associated protein (Arc), Cyclic AMP-Responsive Element-Binding protein 3 (CREB3) and Early Growth Response protein 1 (EGR1) was analyzed by CHIP analysis. Transcription levels of DLG4, Rab11, Arc, CREB3 and EGR1 were detected by quantitative real-time RT-PCR (qRT-PCR).
Results: Methylation levels of DLG4 and Rab11 and hydroxymethylation levels of Arc, Creb3 and Erg1 in patients with somnipathy were significantly higher than those in control group (p<0.01). Increased transcription levels of DLG4, Arc and Erg1, and decreased transcription levels of Rab11 and Creb3 were found in patients with somnipathy than in patients without somnipathy. Transcription level of DLG4 was positively, and Rab11 was negatively correlated with their methylation levels. Transcription levels of Arc and Erg1 were positively, and transcription level of Creb3 was negatively correlated with hydroxymethylation levels.
Conclusion: Increased methylation levels of DLG4 and Rab11 and hydroxymethylation levels of Arc, Creb3 and Erg1 were related to the development of type 2 diabetes in patients with somnipathy. Methylation and hydroxymethylation can significantly affect gene expression at transcription level.