Methylation of Specific CpG Sites in IL-1β and IL1R1 Genes is Affected by Hyperglycaemia in Type 2 Diabetic Patients

ABSTRACT

Objective: Type 2 diabetes (T2D), which is the most common metabolic disorder in the world, results from insulin resistance of target tissues and reduced production of insulin from pancreatic β cells with genetic and environmental factors both playing roles in the pathogenesis. The aim of this study was to investigate the effect of blood glucose levels on DNA methylation of IL-1β and IL1R1 genes in the peripheral blood mononuclear cells (PBMCs) of non-diabetic, type 2 pre-diabetic and diabetic individuals.

Methods: In this case-control study, 54 non-diabetic, pre-diabetic and type 2 diabetic individuals were enrolled and categorized based on their fasting plasma glucose (FPG) and glycated hemoglobin (A1C) levels. DNA was extracted from PBMCs and subjected to bisulfite treatment. The methylation status of two CpG sites in the IL-1β gene and three CpG sites in IL1R1 gene was then determined using Sanger sequencing.

Results: Our results show that the methylation of IL-1β gene is decreased and the methylation of IL1R1 gene is increased in diabetic individuals with hyperglycemia. Further analysis revealed that both CpG sites in IL-1β gene are affected by hyperglycemia and display decreased methylation while only one CpG site in IL1R1 gene is affected by hyperglycemia.

Conclusion: We propose that the DNA methylation status of the CpG sites cg18773937 and cg23149881 in IL-1β gene and the CpG site cg13399261 in IL1R1 gene could serve as an epigenetic marker of chronic inflammation and T2D development. These CpG sites can also be considered for studies on metabolic memory.

KEYWORDS:

• DNA methylation
• epigenetics
• IL-1β pathway
• metabolic memory
• Type 2 diabetes

Acknowledgments

We thank Iranian Society of Diabetes and the clinics of the University of Tehran for providing us with blood samples.

Authors’ contribution

NR carried out the experiments, analyzed the data and wrote the paper. VH-Z designed the project, helped to analyze the data and wrote the paper.

Declaration of interest

There is no conflict of interest to declare. We have full control of all primary data and we agree to allow the journal to review our data if requested.

Supplementary material

Supplemental data for this article can be accessed here.