Submitted: 07 Mar 2019
Accepted: 20 May 2019
ePublished: 18 Jun 2019
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J Renal Inj Prev. 2019;8(3): 175-184.
doi: 10.15171/jrip.2019.33

Scopus ID: 85072586876
  Abstract View: 2291
  PDF Download: 1270


Association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C>T and 1298A>C polymorphisms and the risk of diabetic nephropathy; a meta-analysis

Akriti Gupta 1 ORCID logo, Shubhangi Sharma 2 ORCID logo, Saikrishna Lakkakula 3 ORCID logo, Lakkakula VKS Bhaskar 1* ORCID logo

1 Sickle Cell Institute Chhattisgarh, Raipur, India
2 Department of Biotechnology, Pt. J. N. M. Medical College, Raipur, India
3 Department of Zoology, Visvodaya Government Degree College, Venkatagiri, India
*Corresponding Author: *Corresponding author: Bhaskar VKS Lakkakula, Email: , Email: lvksbhaskar@gmail.com


Methylenetetrahydrofolate reductase (MTHFR) is involved in the homocysteine metabolism. Two common variants of MTHFR gene (677C>T and 1298A>C), have been reported to reduce the MTHFR enzyme activity and leading to plasma hyperhomocysteinemia. There are a number of recent case-control studies that investigated the association between the MTHFR polymorphism and diabetic nephropathy (DN), albeit with inconsistent results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of MTHFR with susceptibility to DN. A literature search was conducted on PubMed, Embase and Google scholar from inception till March 18, 2019. For MTHFR 677C>T analysis, a total of 23 studies including DM controls (3095 cases and 3187 DM controls) and 12 studies including non-DM controls (1590 cases and 2052 nonDM controls) were taken. For MTHFR 1298A>C analysis, a total of 7 studies using DM controls (959 cases and 1209 DM controls) and 3 studies using non-DM controls (400 cases and 802 nonDM controls) were taken. Meta-analysis showed that mutant genotypes of the 677C>T (OR: 1.58; 95%CI: 1.16-2.14) and 1298A>C (OR: 1.38; 95%CI: 1.16-1.65) polymorphisms in the MTHFR gene were associated with increased risk of DN (diabetic kidney disease). MTHFR 677C>T and 1298A>C polymorphisms revealed significant heterogeneity between studies. Further, there was no evidence for publication bias for these polymorphisms. In conclusion, this meta-analysis provides strong evidence that MTHFR 677C>T and 1298A>C polymorphisms may be associated with increased risks of DN. However, further studies are still needed to accurately determine whether MTHFR genetic polymorphisms are associated with susceptibility to DN.

Implication for health policy/practice/research/medical education:

Diabetic nephropathy (DN) (diabetic kidney disease) is the leading cause of chronic kidney disease and is characterized by the albuminuria. Homocysteine levels have been found elevated in patients with DN. The methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in the homocysteine metabolism. MTHFR gene polymorphisms were analyzed in many studies, but their results are inconclusive. We performed a meta-analysis of MTHFR 677C>T and 1298A>C studies. Our results support the association of MTHFR 677C>T and 1298A>C variants with the risk of DN.

Please cite this paper as: Gupta A, Sharma S, Lakkakula S, Bhaskar LV. Association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C>T and 1298A>C polymorphisms and the risk of diabetic nephropathy; a meta-analysis. J Renal Inj Prev. 2019;8(3):175-184. DOI: 10.15171/jrip.2019.33.

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