超氧化物歧化酶基因表达和启动子甲基化作为2型糖尿病的生物标志物

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene Pub Date : 2025-05-26 DOI:10.1016/j.humgen.2025.201427

Ashwin Kumar Shukla , Komal Awasthi , Kauser Usman , Monisha Banerjee

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引用次数: 0

摘要

背景2型糖尿病（T2DM）与氧化应激和基因表达改变有关，尤其是抗氧化防御基因SOD1和SOD2。这些酶在减轻氧化损伤中起着重要的作用，它们的调节可能受到表观遗传修饰（包括DNA甲基化）的显著影响。目的研究T2DM患者启动子SOD1和SOD2基因甲基化状态及表达水平，探讨其作为T2DM分子生物标志物的潜力。方法入选T2DM患者84例，健康对照60例。采用甲基化特异性PCR （methyl- specific PCR， MSP）研究SOD1和SOD2基因启动子甲基化状态，real-time PCR检测SOD1和SOD2基因在全血样本中的表达水平。对T2DM组与对照组的结果进行统计学分析。结果研究显示，与对照组相比，T2DM患者中SOD1和SOD2基因表达均显著下调，两种基因的p值均为0.001。甲基化分析表明，T2DM受试者启动子SOD2甲基化增加，而SOD1甲基化状态无显著差异。结论：我们的研究结果强调了SOD1和SOD2表达降低在T2DM相关氧化应激中的关键作用。虽然观察到SOD2下调，但在患者和对照组之间甲基化频率缺乏显着差异，这表明它本身可能不是一个明确的生物标志物。因此，甲基化对SOD2转录的潜在影响值得进一步研究。了解这些机制可能会导致新的治疗策略针对氧化应激在糖尿病的管理，同时提高我们对代谢疾病中表观遗传因素的作用的认识。

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

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.

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来源期刊

Human Gene Biochemistry, Genetics and Molecular Biology (General), Genetics

CiteScore

1.60

自引率

0.00%

发文量

审稿时长

54 days