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

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 non-dm 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 non-dm 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.