Association of MTHFR C677T polymorphism and type 2 diabetes mellitus (T2DM) susceptibility

Mol Genet Genomic Med. 2019 Dec;7(12):e1020. doi: 10.1002/mgg3.1020. Epub 2019 Oct 30.


Introduction: Methylenetetrahydrofolate reductase (MTHFR) is essential in mediating folate metabolism, and thus plays an important role in diabetes and diabetic complications. MTHFR C677T (rs1801133 C>T) polymorphism has been proposed to be linked with type 2 diabetes mellitus (T2DM) susceptibility. However, the conclusions are inconsistent. Therefore, we rechecked their linkage aiming to obtain a more reliable estimation by performing an updated meta-analysis.

Methods: We searched electronic databases PubMed, EMBASE, CNKI, and Wanfang to obtain studies updated to October 2019.

Results: After carefully screening, we finally incorporated 68 studies with 10,812 cases and 8,745 controls. The genotype frequency of C677T polymorphism was analyzed pooled to generate odds ratios (ORs) and 95% confidence intervals (CIs). Pooled results presented that MTHFR C677T polymorphism was significantly associated with T2DM under homozygous (OR = 1.64, 95% CI = 1.39-1.94), heterozygous (OR = 1.38, 95% CI = 1.20-1.59), recessive (OR = 1.41, 95% CI = 1.23-1.61), dominant (OR = 1.47, 95% CI = 1.27-1.70), and allele (OR = 1.37, 95% CI = 1.23-1.52) genetic models. Stratified analysis demonstrated that C677T genotype was associated with T2DM in Asian populations, but not Caucasian and African populations.

Conclusion: Our results indicated that MTHFR C677T polymorphism confers to T2DM, especially in Asian populations. Much more large-scale case-control studies are needed to strengthen such conclusion in the future.

Keywords: MTHFR; C677T; T2DM; meta-analysis; polymorphism.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*


  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)

Associated data

  • GENBANK/NM_005957.5