Begum Farhana, Lakshmanan Karpagavel
Department of Biochemistry, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, 603103, Tamil Nadu, India.
Biochem Genet. 2024 Sep 12. doi: 10.1007/s10528-024-10910-6.
Diabetic nephropathy (DN) is one of the common complications of type 2 diabetes mellitus (T2DM), and oxidative stress plays a key role in the pathogenesis of DN. Studies have demonstrated that antioxidants (MnSOD, CAT, and GPx1) may reduce the complications associated with T2DM. The purpose of the study is to correlate the role of antioxidant gene polymorphisms in the pathogenesis of DN among T2DM individuals in the South Indian population. It clarifies the importance of early manifestation and reliable genetic indicators modulating the oxidative stress mechanism in DN. The study participants were divided and grouped as Group 1: Control, Group 2: T2DM without DN, and Group 3: T2DM with DN (n = 100 in each group). The levels of plasma glucose, HbA1c, renal profile, SOD, CAT, GPx1, MDA, and TAS were assessed. MnSOD (rs4880), CAT (rs1049982), and GPx1 (rs1050450) polymorphisms were genotyped via Tetra-arms PCR. The genotypes of GPx1 depict a significant role in the progression of DN in T2DM patients (co-dominant [OR: 2.134; 95% CI (1.202-3.788), p < 0.01], dominant [OR: 2.015; 95% CI (1.117-3.634), p = 0.02], and recessive model [OR: 2.215; 95% CI (1.235-3.972), p = 0.008]); whereas rs4880 and rs1049982 polymorphisms are not associated with DN progression. As a result, GPx1 (rs1050450) polymorphism could be a diagnostic risk factor for developing DN in T2DM patients. Moreover, the genotypes of rs4880 and rs1049982 polymorphism show significant difference in the antioxidant parameters compared to the genotypes of rs1050450. In contradiction to earlier studies, the current study demonstrates that the genotypes of rs1050450 (GPx1) can be considered as an influential component for higher susceptibility and risk of developing DN in T2DM patients among the South Indian population.
糖尿病肾病（DN）是2型糖尿病（T2DM）常见的并发症之一，氧化应激在DN的发病机制中起关键作用。研究表明，抗氧化剂（锰超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶1）可能会减少与T2DM相关的并发症。本研究的目的是探讨抗氧化基因多态性在南印度人群T2DM个体DN发病机制中的作用。本研究阐明了DN早期表现的重要性以及调节DN氧化应激机制的可靠遗传指标。研究参与者被分为三组：第1组：对照组；第2组：无DN的T2DM患者；第3组：有DN的T2DM患者（每组n = 100）。评估了血浆葡萄糖、糖化血红蛋白、肾功能指标、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶1、丙二醛和总抗氧化能力水平。通过四臂PCR对锰超氧化物歧化酶（rs4880）、过氧化氢酶（rs1049982）和谷胱甘肽过氧化物酶1（rs1050450）多态性进行基因分型。谷胱甘肽过氧化物酶1的基因型在T2DM患者DN进展中起重要作用（共显性[比值比：2.134；95%可信区间（1.202 - 3.788），p < 0.01]，显性[比值比：2.015；95%可信区间（1.117 - 3.634），p = 0.02]，隐性模型[比值比：2.215；95%可信区间（1.235 - 3.972），p = 0.008]）；而rs4880和rs1049982多态性与DN进展无关。因此，谷胱甘肽过氧化物酶1（rs1050450）多态性可能是T2DM患者发生DN的诊断风险因素。此外，与rs1050450基因型相比，rs4880和rs1049982多态性的基因型在抗氧化参数上有显著差异。与早期研究相反，本研究表明，在南印度人群中，rs1050450（谷胱甘肽过氧化物酶1）基因型可被视为T2DM患者发生DN易感性和风险较高的一个影响因素。
