Deng Guoxiong, Feng Ziyi, Kong Xiaomu, Gao Peng, Jiang Yongwei, Liu Yi, Zhao Meimei, Ma Liang
China-Japan Friendship Institute of Clinical Medicine Research, China-Japan Friendship Hospital, Beijing, China.
Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China.
J Diabetes Res. 2025 Jul 15;2025:8096423. doi: 10.1155/jdr/8096423. eCollection 2025.
The objective of this study is to explore the association between DNA methylation and diabetic kidney disease (DKD). This study involved 120 healthy people, 200 diabetes mellitus (DM) patients, and 200 DKD patients who visited China-Japan Friendship Hospital from 2022 to 2023. We selected four CpG islands for the detection of DNA methylation: three located in the promoter region and one in Exon 2. The methylation rate of the gene was measured using an enzyme digestion method combined with quantitative PCR. Clinical and biochemical characteristics between the two groups were also collected. The methylation rate of the three CpG islands in the promoter region showed no significant differences between the DM and DKD patients. However, a significant difference in the CpG island methylation rate of the gene Exon 2 was observed (25.14% vs. 21.94%, < 0.001). Logistic regression analysis indicated that the methylation rate of Exon2 is negatively associated with the occurrence and progression of DKD (OR = 0.947, 95% CI [0.919, 0.977], = 0.001), with adjustments for gender, age, BMI, smoking, drinking, CHO, and TG. Significant differences were observed in the methylation ratios in different HCY groups (24.51% vs. 21.99%, = 0.031). Linear regression showed Exon 2 methylation negatively correlated with homocysteine (HCY) levels ( = 0.007). Methylation of the gene Exon 2 is a protective factor for DKD and may contribute to its onset and progression through its influence on HCY levels. These findings highlight the potential of methylation as a biomarker for DKD.
本研究的目的是探讨DNA甲基化与糖尿病肾病（DKD）之间的关联。本研究纳入了2022年至2023年期间就诊于中日友好医院的120名健康人、200名糖尿病（DM）患者和200名DKD患者。我们选择了四个CpG岛用于检测DNA甲基化：三个位于启动子区域，一个位于外显子2。采用酶切法结合定量PCR测定该基因的甲基化率。同时收集两组患者的临床和生化特征。启动子区域的三个CpG岛的甲基化率在DM患者和DKD患者之间无显著差异。然而，观察到该基因外显子2的CpG岛甲基化率存在显著差异（25.14%对21.94%，P<0.001）。逻辑回归分析表明，外显子2的甲基化率与DKD的发生和进展呈负相关（OR = 0.947，95%CI[0.919, 0.977]，P = 0.001），并对性别、年龄、BMI、吸烟、饮酒、CHO和TG进行了校正。不同同型半胱氨酸（HCY）组的甲基化率存在显著差异（24.51%对21.99%，P = 0.031）。线性回归显示外显子2甲基化与同型半胱氨酸（HCY）水平呈负相关（P = 0.007）。该基因外显子2的甲基化是DKD的保护因素，可能通过影响HCY水平对其发病和进展产生作用。这些发现突出了该甲基化作为DKD生物标志物的潜力。
