Association of MTHFR Gene with Type 2 Diabetes Mellitus: A Case-Control Study and Meta-Analysis.

Introduction: Multiple studies have shown that genetic polymorphism in the MTHFR gene is associated with susceptibility to type 2 diabetes mellitus (T2DM), but the results remain controversial. This study was divided into two parts. The first part was to explore the relationship between the SNPs of MTHFR gene (C677T and A1298C) and genetic susceptibility to T2DM. Second, a meta-analysis was performed to evaluate the association between C677T gene and T2DM.

Methods: A case-control study was conducted to assess the association of MTHFR polymorphisms with T2DM risk. A meta-analysis including 7 studies was conducted by using Stata 17.0 software.

Results: In case-control study at the C677T (rs1801133), we found that compared with the AA genotype, GG + GA genotype was associated with an increased risk of T2DM (OR = 1.605; 95% CI: 1.229-2.095; p = 0.001); compared with the GG/GA genotype, AA genotype was associated with a decreased risk of T2DM (OR = 0.620; 95% CI: 0.450-0.855; p = 0.004; OR = 0.625; 95% CI: 0.470-0.830; p = 0.001). After adjusting for age, gender, and BMI statistical differences persisted. In case-control study at the A1298C (rs1801131), there was no significant association in all genetic models after adjusting for age, gender, and BMI. In the overall meta-analysis of the C677T gene, significant heterogeneity was detected in the recessive model (I2 = 89.84%, p < 0.01) and allele model (I2 = 88.38%, p < 0.01). Subgroup analysis showed that there was a significant association in the recessive model (I2 = 76.52%, p < 0.01; OR = 2.27, 95% CI: 1.16-4.44) under random-effects models in Asians.

Conclusions: The results suggest that the C677T polymorphism might have ethnicity-dependent effects in T2DM and may be associated with susceptibility to T2DM in Asians.