Download PDF
Horm Metab Res 2022; 54(12): 845-851
DOI: 10.1055/a-1945-3036
Original Article: Endocrine Care

The Association of Methylenetetrahydrofolate Reductase (MTHFR) A1298C Gene Polymorphism with Susceptibility to Diabetic Nephropathy: A Meta-Analysis

Yanhong Huo
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
,
Wenbo Zhang
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
,
Xin Zhang
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
,
Li Su
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
,
Hao Li
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
,
Fa Wang
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
,
Yan Zhang
2   Department of Ophthalmology, Chinese People’s Liberation Army General Hospital, Beijing, China
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

This meta-analysis was conducted to investigate the association between MTHFR A1298C polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI) and China Wanfang database were searched for studies on the association between MTHFR A1298C single nucleotide polymorphism and susceptibility to diabetic nephropathy until May 2022. Data were analyzed by Stata 15.0 software. Odds ratio (OR) was used as the effect size. A total of 7 articles were identified, including 1287 cases in the diabetic nephropathy group and 1431 cases in the control group. The pooled OR of allele C at MTHFR A1298C was 1.28 (95% CI: 1.02–1.59, p=0.03) compared with allele A. The pooled OR values of dominant, and heterozygous genetic models were 1.45 (95% CI: 1.13–1.86), and 1.42 (95% CI: 1.19–1.70), respectively, and the differences were all statistically significant. There was no statistical significance in the recessive (OR=1.06, 95% CI: 0.62–1.82), and homozygous gene inheritance models (OR=1.29, 95% CI: 0.72–2.31). In conclusion, MTHFR A1298C polymorphism is associated with susceptibility to diabetic nephropathy. Allele C, genotype CC+AC, and AC at MTHFR A1298C locus can increase the risk of diabetic nephropathy.

Key words

diabetic complications, diabetes - diabetic nephropathy - diabetic retinopathy


Publication History

Received: 03 June 2022

Accepted after revision: 14 September 2022

Accepted Manuscript online:
15 September 2022

Article published online:
20 October 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Willis M, Nilsson A, Kellerborg K. et al. Cost-effectiveness of canagliflozin added to standard of care for treating diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) in England: estimates using the CREDEM-DKD model. Diabetes Ther 2021; 12: 313-328
    CrossrefPubMedGoogle Scholar
  • 2 Huang JX, Liao YF, Li YM. Clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus. Curr Med Sci 2019; 39: 754-758
    CrossrefPubMedGoogle Scholar
  • 3 Dhumad MM, Hamdan FB, Khudhair MS. et al. Correlation of staging and risk factors with cardiovascular autonomic neuropathy in patients with type II diabetes mellitus. Sci Rep 2021; 11: 3576
    CrossrefPubMedGoogle Scholar
  • 4 Bui HDT, Jing X, Lu R. et al. Prevalence of and factors related to microvascular complications in patients with type 2 diabetes mellitus in Tianjin, China: a cross-sectional study. Ann Transl Med 2019; 7: 325
    CrossrefPubMedGoogle Scholar
  • 5 Abe M, Okada K, Maruyama N. et al. Comparison of clinical trajectories before initiation of renal replacement therapy between diabetic nephropathy and nephrosclerosis on the KDIGO guidelines heat map. J Diabetes Res 2016; 5374746
    PubMedGoogle Scholar
  • 6 Nemr R, Salman R, Jawad L. et al. Differential contribution of MTHFR C677T variant to the risk of diabetic nephropathy in Lebanese and Bahraini Arabs. Clin Chem Lab Med 2010; 48: 1091-1094
    CrossrefPubMedGoogle Scholar
  • 7 Mtiraoui N, Ezzidi I, Chaieb M. et al. MTHFR C677T and A1298C Gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients. Diabetes Res Clin Pract 2007; 75: 99-106
    CrossrefPubMedGoogle Scholar
  • 8 Younas H, Ijaz T, Choudhry N. Investigation of angiotensin-1 converting enzyme 2 gene (G8790A) polymorphism in patients of type 2 diabetes mellitus with diabetic nephropathy in Pakistani population. PLoS One 2022; 17: e264038
    CrossrefPubMedGoogle Scholar
  • 9 Buraczynska M, Ksiazek K, Wacinski P. et al. IL1BInterleukin-1β Gene polymorphism and risk of developing diabetic nephropathy. Immunol Invest 2019; 48: 577-584
    CrossrefPubMedGoogle Scholar
  • 10 Poduri A, Kumari S, Jain S. et al. A case-control study of the association between the MTHFR gene and essential hypertension in Asian Indians. J Hum Hypertens 2009; 23: 140-142
    CrossrefPubMedGoogle Scholar
  • 11 Blom HJ, Milos R, Goyette P. et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-113
    CrossrefPubMedGoogle Scholar
  • 12 NMJV Put, Gabre LsF, Stevens EMB. et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?. Am J Hum Genet 1998; 62: 1044-1051
    CrossrefPubMedGoogle Scholar
  • 13 Guan H, Xia MD, Wang M. et al. Methylenetetrahydrofolate reductase genetic polymorphism and the risk of diabetic nephropathy in type 2 diabetic patients. Medicine 2020; 99: e21558
    CrossrefPubMedGoogle Scholar
  • 14 Moher D, Liberati A, Tetzlaff J. et al. Methods of systematic reviews and meta-analysis preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 8: 336-341
    PubMedGoogle Scholar
  • 15 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-605
    CrossrefPubMedGoogle Scholar
  • 16 Rahimi M, Hasanvand A, Rahimi Z. et al. Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus. Clin Biochem 2011; 43: 1333-1339
    CrossrefPubMedGoogle Scholar
  • 17 El-Baz R, Settin A, Ismaeel A. et al. MTHFR C677T, A1298C and ACE I/D polymorphisms as risk factors for diabetic nephropathy among type 2 diabetic patients. J Renin Angiotensin Aldosterone Syst 2012; 13: 472
    CrossrefPubMedGoogle Scholar
  • 18 Ramanathan G, Harichandana B, Kannan S. et al. Association between end-stage diabetic nephropathy and MTHFR (C677T and A1298C) gene polymorphisms. Nephrology (Carlton) 2019; 14: 155-159
    CrossrefPubMedGoogle Scholar
  • 19 Yu G, Zheng YP, Shen J. The correlation between genetic polymorphism of methyltetrahydrofolate reductase and type 2 diabetic nephropathy. Labeled Immunoassays. Clin Med 2020; 27: 2079-2082
    PubMedGoogle Scholar
  • 20 Shpichinetsky V, Raz I, Friedlander Y. et al. The association between two common mutations C677T and A1298C in human methylenetetrahydrofolate reductase gene and the risk for diabetic nephropathy in type II diabetic patients1. J Nutr 2000; 130: 2493-2497
    CrossrefPubMedGoogle Scholar
  • 21 Dos Santos Nunes MK, Silva AS, de Queiroga Evangelista IW. et al. MTHFR Hypermethylation in the promoter of the gene is associated with diabetic complications and biochemical indicators. Diabetol Metab Syndr 2017; 9: 84
    CrossrefPubMedGoogle Scholar
  • 22 Yang XH, Cao RF, Yu Y. et al. A study on the correlation between MTHFR promoter methylation and diabetic nephropathy. Am J Transl Res 2016; 8: 4960-4967
    PubMedGoogle Scholar
  • 23 Santana Bezerra H, de Assis CS, Dos Santos Nunes MK. et al. MTHFR The promoter hypermethylation pattern associated with the A1298C polymorphism influences lipid parameters and glycemic control in diabetic patients. Diabetol Metab Syndr 2019; 11: 4
    CrossrefPubMedGoogle Scholar
  • 24 Zhang J, Xiao Y, Zhang X. et al. Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy risk: a meta-analysis. Ren Fail 2014; 36: 974-978
    CrossrefPubMedGoogle Scholar