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. 2025 Jul 15:2025:8096423.
doi: 10.1155/jdr/8096423. eCollection 2025.

Association Between DNA Methylation of MTHFR and Diabetic Kidney Disease

Guoxiong Deng  1   2 , Ziyi Feng  1   2 , Xiaomu Kong  2 , Peng Gao  2 , Yongwei Jiang  2 , Yi Liu  2 , Meimei Zhao  2 , Liang Ma  2
Affiliations

Association Between DNA Methylation of MTHFR and Diabetic Kidney Disease

Guoxiong Deng et al. J Diabetes Res. .

Abstract

Objective: The objective of this study is to explore the association between MTHFR DNA methylation and diabetic kidney disease (DKD). Methods: 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 MTHFR DNA methylation: three located in the promoter region and one in Exon 2. The methylation rate of the MTHFR gene was measured using an enzyme digestion method combined with quantitative PCR. Clinical and biochemical characteristics between the two groups were also collected. Results: 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 MTHFR gene Exon 2 was observed (25.14% vs. 21.94%, p < 0.001). Logistic regression analysis indicated that the methylation rate of MTHFR Exon2 is negatively associated with the occurrence and progression of DKD (OR = 0.947, 95% CI [0.919, 0.977], p = 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%, p = 0.031). Linear regression showed MTHFR Exon 2 methylation negatively correlated with homocysteine (HCY) levels (p = 0.007). Conclusion: Methylation of the MTHFR 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 MTHFR methylation as a biomarker for DKD.

Keywords: DKD; DNA methylation; HCY; MTHFR.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The principle of methylation rate detection and the target region. (a) Principle of enzyme digestion detection. DNA methylation will block the digestion of HpaII, while the digestion of MspI will not be influenced. (b) According to the distribution of CpG islands, we choose four targets to detect. Three of them are in the promoter region (P-1, P-2, and P-3), and one is in Exon 2 (E-1).
Figure 2
Figure 2
Methylation rate of MTHFR Exon 2 in different HCY group patients.
See this image and copyright information in PMC

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