Akriti Gupta
1 
, Shubhangi Sharma
2 , Saikrishna Lakkakula
3 , Lakkakula VKS Bhaskar
1* 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
Abstract
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.