Type 2 Diabetes Mellitus (T2DM) is well known to include an inflammatory component that has been considered to be related to diabetic complications. Diabetic nephropathy (DN) is one of the significant complications as it constitutes the most frequent cause of end-stage renal disease. Tumor Necrosis Factor-α (TNF-α) is known as a multifunctional proinflammatory cytokine which is associated with some pathological processes such as immunoregulation, proliferation, inflammation, and apoptosis. The aim was to explore the association between the TNF-α promoter -1031T/C single nucleotide polymorphism (SNP) and the serum TNF-α level in addition to nephropathy among type 2 diabetic patients. The study included 38 T2DM subjects without nephropathy (DM group), 40 subjects with DN, and 20 controls. Identification of TNF-α promoter gene polymorphism -1031T/C was done by PCR-RFLP, and genotyping was confirmed by direct sequencing. The serum TNF-α level was assessed by ELISA. Correlations were tested by Pearson’s correlation analysis. Logistic regression was used to detect the most independent factor for development of DN. The serum level of TNF-α in the DM group was significantly higher than controls (); also, the DN group was considerably higher than controls and DM without nephropathy (). Also, there was a significant positive correlation between serum levels of TNF-α with FBG (fasting blood glucose), creatinine, total cholesterol, LDL-C, HbA1c, and microalbumin/creatinine ratio (ACR) among the DN group (, <0.001, <0.001, <0.001, 0.027, and 0.043, respectively). Mutant homozygous CC and heterozygous TC genotypes were higher in DN than in DM and controls. C allele was more represented in DN than in DM and controls () while T allele was higher in controls than in DM and DN patients. The levels of TNF-α were higher in subjects who had mutant CC than the wild TT genotype among DN (). C allele was more risky for DN than T allele between DN and controls by 5.4-fold (CI: 1.75-16.68) as well as between DN and DM by 2.25-fold (CI: 1.1-4.59). Conclusion. Serum levels of TNF-α were higher in individuals with mutant CC genotype of -1031T/C TNF-α gene, and C allele could be associated with increased risk for nephropathy among patients with T2DM.

中文翻译：

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研究肿瘤坏死因子启动子多态性与 2 型糖尿病肾病的关联。


众所周知，2 型糖尿病 (T2DM) 包含一种被认为与糖尿病并发症相关的炎症成分。糖尿病肾病（DN）是重要的并发症之一，因为它是终末期肾病的最常见原因。肿瘤坏死因子-α （TNF- α ）被称为多功能促炎细胞因子，与免疫调节、增殖、炎症和细胞凋亡等一些病理过程相关。目的探讨2型糖尿病患者TNF- α启动子-1031T / C单核苷酸多态性(SNP)与血清TNF- α水平及肾病的关系。该研究包括 38 名无肾病的 T2DM 受试者（DM 组）、40 名 DN 受试者和 20 名对照者。通过PCR-RFLP鉴定TNF- α启动子基因多态性——1031T / C ，并通过直接测序确认基因分型。通过ELISA评估血清TNF- α水平。通过 Pearson 相关分析测试相关性。 Logistic回归用于检测DN发生的最独立因素。 DM组血清TNF- α水平显着高于对照组（ ）；此外，DN 组显着高于对照组和无肾病的 DM 组（ ）。此外，DN 组中血清 TNF- α水平与 FBG（空腹血糖）、肌酐、总胆固醇、LDL-C、HbA1c 和微量白蛋白/肌酐比值 (ACR) 呈显着正相关。 , <0 id=67> ）而对照组中的 T 等位基因高于 DM 和 DN 患者。 DN 中，突变 CC 受试者的 TNF- α水平高于野生 TT 基因型受试者（ ）。 DN 与对照之间，C 等位基因对 DN 的风险比 T 等位基因高 5.4 倍（CI：1.75-16.68），在 DN 与 DM 之间则高 2.25 倍（CI：1.1-4.59）。结论。 - 1031T / C TNF- α基因突变CC基因型个体的血清TNF- α水平较高，C等位基因可能与T2DM患者肾病风险增加有关。