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

Abstract

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.