Methylenetetrahydrofolate Reductase Genetic Polymorphism and the Risk of Diabetic Nephropathy in Type 2 Diabetic Patients

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2020 Sep 3

PMID 32871871

Citations 5

Authors

Hui Guan

Meng-Di Xia

Miao Wang

Ying-Jie Guan

Xiao-Chen Lyu

Affiliations

Soon will be listed here.

Abstract

Background: As indicated by numerous studies, there exists a relationship between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to diabetic nephropathy (DN) in various populations; nonetheless, the findings remain inconsistent. Therefore, we carried out a meta-analysis to determine the relationship between the MTHFR gene polymorphism and DN susceptibility.

Materials And Method: Related studies were identified from PubMed, Cochrane Library, EMBASE, and the China National Knowledge Infrastructure database (time period: from building the library to October 2019). The strength of the association was examined using odds ratios (ORs) with 95% confidence intervals (95% CIs).

Results: The findings illustrated that the C677T gene polymorphism was significantly associated with an enhanced susceptibility to DN compared to that with diabetes mellitus in allelic (OR = 1.64, 95% CI = 1.34-2.00, P < .001), dominant (OR = 1.85, 95% CI = 1.40-2.46, P < .001), codominant (heterozygote: OR = 1.67, 95% CI = 1.27-2.21, P < .001; homozygote: OR = 2.55, 95% CI = 1.82-3.57, P < .001), and recessive (OR = 1.89, 95% CI = 1.50-2.38, P < .001) models of the overall population. Moreover, as compared with the healthy controls, a significantly augmented susceptibility to DN was found in all 5 genetic comparison models (allelic: OR = 2.06, 95% CI = 1.58-2.67, P < .001; dominant: OR = 2.52, 95% CI = 1.73-3.69, P < .001; codominant: OR = 3.78, 95% CI = 2.50-5.70, P < .001; recessive: OR = 2.41, 95% CI = 1.96-2.97, P < .001). Furthermore, stratifying data by ethnicity revealed substantially augmented vulnerability to DN in not only Caucasian but also Asian populations.

Conclusion: The present study suggests that the C677T polymorphism was associated with an augmented susceptibility to DN.

Citing Articles

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References

Mantel N, Haenszel W . Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959; 22(4):719-48. View

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

Yoshioka K, Yoshida T, Umekawa T, Kogure A, Takakura Y, Toda H . Methylenetetrahydrofolate reductase gene polymorphism is not related to diabetic nephropathy in Japanese Type 2 diabetic patients. Diabet Med. 2004; 21(9):1051-2. DOI: 10.1111/j.1464-5491.2004.01192.x. View

DerSimonian R, Laird N . Meta-analysis in clinical trials revisited. Contemp Clin Trials. 2015; 45(Pt A):139-45. PMC: 4639420. DOI: 10.1016/j.cct.2015.09.002. View

Shcherbak N, Shutskaya Z, Sheidina A, Larionova V, Schwartz E . Methylenetetrahydrofolate reductase gene polymorphism as a risk factor for diabetic nephropathy in IDDM patients. Mol Genet Metab. 1999; 68(3):375-8. DOI: 10.1006/mgme.1999.2909. View

Begg C, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50(4):1088-101. View

Fowler B . Disorders of homocysteine metabolism. J Inherit Metab Dis. 1997; 20(2):270-85. DOI: 10.1023/a:1005369109055. View

Arneth B, Arneth R, Shams M . Metabolomics of Type 1 and Type 2 Diabetes. Int J Mol Sci. 2019; 20(10). PMC: 6566263. DOI: 10.3390/ijms20102467. View

Meza Letelier C, San Martin Ojeda C, Ruiz Provoste J, Frugone Zaror C . [Pathophysiology of diabetic nephropathy: a literature review]. Medwave. 2017; 17(1):e6839. DOI: 10.5867/medwave.2017.01.6839. View

10.

Ksiazek P, Bednarek-Skublewska A, Buraczynska M . The C677T methylenetetrahydrofolate reductase gene mutation and nephropathy in type 2 diabetes mellitus. Med Sci Monit. 2004; 10(2):BR47-51. View

11.

Xue R, Gui D, Zheng L, Zhai R, Wang F, Wang N . Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective. J Diabetes Res. 2017; 2017:1839809. PMC: 5366800. DOI: 10.1155/2017/1839809. View

12.

Bluthner M, Bruntgens A, Schmidt S, Strojek K, Grzeszczak W, Ritz E . Association of methylenetetrahydrofolate reductase gene polymorphism and diabetic nephropathy in type 2 diabetes?. Nephrol Dial Transplant. 1999; 14(1):56-7. DOI: 10.1093/ndt/14.1.56. View

13.

Rahimi Z, Hasanvand A, Felehgari V . Interaction of MTHFR 1298C with ACE D allele augments the risk of diabetic nephropathy in Western Iran. DNA Cell Biol. 2011; 31(4):553-9. DOI: 10.1089/dna.2011.1364. View

14.

Wang L, Wang J, Xue Y, Chen Y, Zou H . [Relationship between methylenetetrahydrofolate reductase gene polymorphism and diabetic nephropathy]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2001; 18(4):276-8. View

15.

Zintzaras E, Ioannidis J . HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics. 2005; 21(18):3672-3. DOI: 10.1093/bioinformatics/bti536. View

16.

Thomas M, Cooper M, Zimmet P . Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2015; 12(2):73-81. DOI: 10.1038/nrneph.2015.173. View

17.

Ramanathan G, Harichandana B, Kannan S, Elumalai R, Sfd P . Association between end-stage diabetic nephropathy and MTHFR (C677T and A1298C) gene polymorphisms. Nephrology (Carlton). 2017; 24(2):155-159. DOI: 10.1111/nep.13208. View

18.

Ma L, Jiang Y, Kong X, Liu Q, Zhao H, Zhao T . Interaction of MTHFR C677T polymorphism with smoking in susceptibility to diabetic nephropathy in Chinese men with type 2 diabetes. J Hum Genet. 2018; 64(1):23-28. DOI: 10.1038/s10038-018-0531-y. View

19.

Mtiraoui N, Ezzidi I, Chaieb M, Marmouche H, Aouni Z, Chaieb A . MTHFR C677T and A1298C gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients. Diabetes Res Clin Pract. 2006; 75(1):99-106. DOI: 10.1016/j.diabres.2006.05.018. View

20.

Xiong X, Lin X, Xiao X, Qin D, Zhou D, Hu J . Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta-analysis and review. Nephrology (Carlton). 2015; 21(1):5-12. DOI: 10.1111/nep.12541. View