Superoxide dismutase gene expression and promoter methylation as biomarkers for type 2 diabetes mellitus

Abstract

Background

Type 2 diabetes mellitus (T2DM) is associated with oxidative stress and altered gene expression, particularly the antioxidant defense genes named as SOD1 and SOD2. These enzymes serve a significant function in mitigating oxidative damage, and their regulation may be significantly influenced by epigenetic modifications, including DNA methylation.

Objective

This study aimed to investigate the promoter methylation status and expression levels of SOD1 and SOD2 genes in T2DM patients compared to healthy controls, to explore their potential as molecular biomarkers for T2DM.

Methodology

A total of 84 T2DM patients and 60 healthy controls were enrolled. Methylation-specific PCR (MSP) was applied to investigate the promoter methylation status of SOD1 and SOD2 genes, while real-time PCR was utilized to evaluate the expression levels of these genes in whole blood samples. Statistical analyses were performed to compare results between the T2DM group and the control group.

Results

The study revealed significant downregulation of both SOD1 and SOD2 gene expression in T2DM patients compared to controls, with p-values of 0.001 for both genes. Methylation analysis indicated increased promoter methylation of SOD2 in T2DM subjects, whereas SOD1 did not show any significant difference in the methylation status.

Conclusion

Our findings highlighted the critical role of reduced SOD1 and SOD2 expression in oxidative stress associated with T2DM. Although SOD2 downregulation was observed, the lack of significant differences in methylation frequency between patients and controls indicated that it may not serve as a definitive biomarker by itself. Therefore, the potential influence of methylation on SOD2 transcription warrants further investigation. Understanding these mechanisms could lead to novel therapeutic strategies targeting oxidative stress in diabetes management and at the same time improve our knowledge regarding the role of epigenetic factors in metabolic diseases.