Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Mol Biol Rep. 2024 Apr 29;51(1):583. doi: 10.1007/s11033-024-09519-0.
Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications.
In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods.
Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)].
The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.
慢性高血糖中的氧化应激会损伤组织，并引发糖尿病相关并发症，如视网膜病变和神经病变。本研究旨在探讨亚甲基四氢叶酸还原酶（MTHFR）和谷胱甘肽过氧化物酶（GPx）基因变异与这些并发症的关系。
在这项病例对照研究中，研究人员选取了来自伊朗西部的 400 名个体，包括 100 名健康受试者和 300 名 2 型糖尿病患者（T2DM），分为三组：视网膜病变组（n=100）、神经病变组（n=100）和无并发症组（n=100）。采用 PCR-RFLP 法检测 MTHFR（rs1801133）和 GPx-1（rs1050450）的变异情况。通过化学方法测量血浆 GPx 活性、谷胱甘肽、丙二醛（MDA）、总抗氧化能力（TAC）和总氧化应激（TOS）的水平。
与其他患者和对照组相比，神经病变患者的 BMI、TOS 和 MDA 水平更高。与其他组相比，患有神经病变的糖尿病患者的谷胱甘肽（7.8±4.5；P<0.001）、GPx 活性（39.5±8.5；P<0.001）和 TAC（703.1±129.1；P=0.0001）水平更低。无并发症和视网膜病变患者的血浆谷胱甘肽（12.2±2.4；p=0.02）和 TAC（793.4±124.6；P<0.001）水平更高。MTHFR TT 基因型与较低的 TOS（3.5±1.1；P<0.001）和 OSI（0.0050±0.001；P<0.001）水平显著相关。GPx-1 TT 基因型的受试者具有更高的 MDA（6.8±2.5；P=0.02）和较低的 TOS（3.7±1.6；P<0.001）水平，具有统计学意义。MTHFR 的 TT 基因型与神经病变的风险增加 3.9 倍（95%CI 1.04-4.76；P=0.0436）相关。此外，GPx-1 CT 基因型增加了视网膜病变的风险[OR=2.7（95%CI=1.38-5.44；P=0.0039)]。
MTHFR TT 基因型显著增加了糖尿病患者发生神经病变的风险。GPx-1 CT 基因型与糖尿病患者视网膜病变风险增加相关。MTHFR 和 Gpx-1 TT 基因型均与较高的 BMI 水平相关。
