Laboratory for Histology and Genetics of Atherosclerosis and Microvascular Diseases, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia.
Institute of Histology and Embryology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2024 Aug 30;25(17):9439. doi: 10.3390/ijms25179439.
The aim of our study was to investigate an association between polymorphisms of either the (vascular endothelial growth factor) gene (rs6921438) or the (kinase insert domain receptor) gene (rs2071559, rs2305948) and DN (diabetic nephropathy) in Caucasians with T2DM (type 2 diabetes mellitus). The second aim was to investigate the effect of either the gene (rs6921438) or the gene (rs2071559, rs2305948) on the immune expression of either VEGF or KDR in the renal tissues of T2DM subjects (to test the functional significance of tested polymorphisms). The study included 897 Caucasians with T2DM for at least ten years (344 patients with DN and 553 patients without DN). Each subject was genotyped and analyzed for (rs1617640, rs2305948) and (rs6921438) polymorphisms. Kidney tissue samples taken from 15 subjects with T2DM (autopsy material) were immunohistochemically stained for the expression of VEGF and KDR. We found that the rs2071559 gene was associated with an increased risk of DN. In addition, the GG genotype of the rs6921438 gene had a protective effect. We found a significantly higher numerical area density of VEGF-positive cells in T2DM subjects with the A allele of the rs6921438- compared to the homozygotes for wild type G allele (7.0 ± 2.4/0.1 mm vs. 1.24 ± 0.5/0.1 mm, respectively; < 0.001). Moreover, a significantly higher numerical area density of KDR-positive cells was found in T2DM subjects with the C allele of rs2071559 (CC + CT genotypes) compared to the homozygotes for wild type T allele (9.7± 3.2/0.1 mm vs. 1.14 ± 0.5/0.1 mm, respectively; < 0.001) To conclude, our study showed that the presence of the C allele of the rs2071559 gene was associated with a higher risk of DN, while the G allele of the rs6921438- conferred protection against DN in Slovenian T2DM subjects.
我们的研究目的是探讨血管内皮生长因子（VEGF）基因（rs6921438）或激酶插入结构域受体（KDR）基因（rs2071559、rs2305948）的多态性与高加索人 2 型糖尿病（T2DM）合并糖尿病肾病（DN）之间的相关性。第二个目的是研究 VEGF 或 KDR 基因的 rs6921438 或 rs2071559、rs2305948 多态性对 T2DM 患者肾组织中 VEGF 或 KDR 的免疫表达的影响（以检验所研究的多态性的功能意义）。本研究纳入了 897 名至少患病 10 年的高加索人 T2DM 患者（344 例 DN 患者和 553 例无 DN 患者）。对每位患者进行基因分型和分析，以检测 rs1617640、rs2305948 和 rs6921438 多态性。从 15 名 T2DM 患者（尸检材料）的肾脏组织样本中提取免疫组织化学染色 VEGF 和 KDR 的表达。我们发现 rs2071559 基因与 DN 风险增加相关。此外，rs6921438 基因的 GG 基因型具有保护作用。我们发现，与 rs6921438-野生型 G 等位基因纯合子相比，携带 A 等位基因的 T2DM 患者的 VEGF 阳性细胞的数值面积密度明显更高（7.0±2.4/0.1mm 比 1.24±0.5/0.1mm，分别；<0.001）。此外，与 rs2071559 野生型 T 等位基因纯合子相比，携带 rs2071559 基因 C 等位基因的 T2DM 患者的 KDR 阳性细胞的数值面积密度明显更高（CC+CT 基因型）（9.7±3.2/0.1mm 比 1.14±0.5/0.1mm，分别；<0.001）。总之，我们的研究表明，rs2071559 基因的 C 等位基因的存在与斯洛文尼亚 2 型糖尿病患者的 DN 风险增加相关，而 rs6921438-的 G 等位基因则对 DN 具有保护作用。
