Naseri Rozita, Khalili Farnaz, Rahimi Zohreh, Yari Kheirolah, Rezaei Mansour
Department of Internal Medicine Medical School Kermanshah University of Medical Sciences Kermanshah Iran.
Department of Clinical Biochemistry Medical School Kermanshah University of Medical Sciences Kermanshah Iran.
Health Sci Rep. 2024 Oct 28;7(11):e70106. doi: 10.1002/hsr2.70106. eCollection 2024 Nov.
Sirtuin-1 (SIRT1) has antidiabetic effects through the regulation of insulin secretion and modulation of inflammation. The rs3758391 gene polymorphism affects the level of SIRT1. The current study aimed to investigate the possible influence of gene variants in relation to oxidative stress parameters on the susceptibility to type 2 diabetes mellitus (T2DM) and its microvascular complications.
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 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. genotypes were detected using the polymerase chain reaction-restriction fragment length polymorphism method.
The C allele of 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 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.
Our findings suggest a protective role for 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.
沉默信息调节因子1（SIRT1）通过调节胰岛素分泌和炎症反应发挥抗糖尿病作用。rs3758391基因多态性影响SIRT1水平。本研究旨在探讨与氧化应激参数相关的基因变异对2型糖尿病（T2DM）及其微血管并发症易感性的可能影响。
在这项病例对照研究中，对398名个体进行了rs3758391 T>C变异研究，其中包括300例T2DM患者（100例无并发症的T2DM患者、100例糖尿病神经病变患者和100例糖尿病视网膜病变患者）和98名健康受试者。此外，采用比色法测定谷胱甘肽过氧化物酶（GPx）活性、谷胱甘肽（GSH）、丙二醛（MDA）、总抗氧化能力（TAC）和总氧化状态（TOS）水平。使用聚合酶链反应-限制性片段长度多态性方法检测基因型。
rs3758391的C等位基因降低了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，与健康个体相比，患者的MDA水平显著升高。考虑所有个体，与TT基因型相比，CC和TC基因型个体的GPx活性增加。在所有研究个体中，正常体重指数（BMI）受试者的GPx活性显著高于超重和肥胖个体。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的平均水平显著高于BMI正常的患者。
我们的研究结果表明，rs3758391的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。我们发现该等位基因存在时GPx活性增加。此外，我们检测到超重和肥胖的糖尿病患者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。
