Protective role of SIRT1 (rs3758391 T > C) polymorphism against T2DM and its complications: Influence on GPx activity

IF 2.1 Q2 MEDICINE, GENERAL & INTERNAL

Health Science Reports Pub Date : 2024-10-28 DOI:10.1002/hsr2.70106

Rozita Naseri, Farnaz Khalili, Zohreh Rahimi, Kheirolah Yari, Mansour Rezaei

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Abstract

Background and Aims

Sirtuin-1 (SIRT1) has antidiabetic effects through the regulation of insulin secretion and modulation of inflammation. The SIRT1 rs3758391 gene polymorphism affects the level of SIRT1. The current study aimed to investigate the possible influence of SIRT1 gene variants in relation to oxidative stress parameters on the susceptibility to type 2 diabetes mellitus (T2DM) and its microvascular complications.

Methods

In this case-control study 398 individuals including 300 patients with T2DM (100 T2DM without complication, 100 diabetic neuropathy patients and 100 patients with diabetic retinopathy) and 98 healthy subjects were studied for SIRT1 rs3758391 T > C variants. Also, the glutathione peroxidase (GPx) activity and the levels of glutathione (GSH), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative status (TOS) were determined by colorimetric methods. SIRT1 genotypes were detected using the polymerase chain reaction-restriction fragment length polymorphism method.

Results

The C allele of SIRT1 reduced the risk of T2DM, diabetic neuropathy and diabetic retinopathy. Significantly lower levels of GSH, GPx, and TAC were found in diabetic patients compared to control group. However, the level of MDA was significantly higher in patients compared to healthy individuals. Considering all individuals, the GPx activity increased in the presence of the SIRT1 CC, and TC genotypes compared to the TT genotype. Among all studied individuals the activity of GPx was significantly higher in normal body mass index (BMI) subjects than overweight, and obese individuals. However, among overweight and obese diabetic, diabetic retinopathy and diabetic neuropathy patients the mean level of TOS was significantly higher compared to patients with normal BMI.

Conclusions

Our findings suggest a protective role for SIRT1 C allele against T2DM and diabetic neuropathy and diabetic retinopathy. We found in the presence of this allele the GPx activity increased. Also, we detected an enhanced oxidative stress level among overweight and obese patients with diabetes and its complications that could be involved in the pathogenesis of the disease.

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SIRT1（rs3758391 T > C）多态性对 T2DM 及其并发症的保护作用：对 GPx 活性的影响

背景和目的 Sirtuin-1（SIRT1）通过调节胰岛素分泌和炎症反应具有抗糖尿病作用。SIRT1 rs3758391 基因多态性会影响 SIRT1 的水平。本研究旨在探讨 SIRT1 基因变异与氧化应激参数的关系对 2 型糖尿病（T2DM）及其微血管并发症易感性的可能影响。方法在这项病例对照研究中，研究人员对包括 300 名 T2DM 患者（100 名无并发症的 T2DM 患者、100 名糖尿病神经病变患者和 100 名糖尿病视网膜病变患者）和 98 名健康受试者在内的 398 人进行了 SIRT1 rs3758391 T > C 变异研究。此外，还采用比色法测定了谷胱甘肽过氧化物酶（GPx）活性以及谷胱甘肽（GSH）、丙二醛（MDA）、总抗氧化能力（TAC）和总氧化状态（TOS）的水平。采用聚合酶链式反应-限制性片段长度多态性方法检测 SIRT1 基因型。结果 SIRT1 的 C 等位基因可降低 T2DM、糖尿病神经病变和糖尿病视网膜病变的风险。与对照组相比，糖尿病患者的 GSH、GPx 和 TAC 水平显著降低。然而，与健康人相比，患者的 MDA 水平明显较高。就所有个体而言，与 TT 基因型相比，SIRT1 CC 和 TC 基因型的 GPx 活性增加。在所有研究对象中，体重指数（BMI）正常者的 GPx 活性明显高于超重和肥胖者。然而，在超重和肥胖的糖尿病、糖尿病视网膜病变和糖尿病神经病变患者中，TOS 的平均水平明显高于体重指数正常的患者。结论我们的研究结果表明，SIRT1 C 等位基因对 T2DM、糖尿病神经病变和糖尿病视网膜病变具有保护作用。我们发现，在该等位基因存在的情况下，GPx 活性增加。此外，我们还发现超重和肥胖糖尿病及其并发症患者的氧化应激水平升高，这可能与疾病的发病机制有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Health Science Reports Medicine-Medicine (all)

CiteScore

1.80

自引率

0.00%

发文量

458

审稿时长

20 weeks