Determining the Risk of Type 2 Diabetes for rs1801133 Genotypes in Multiethnic Populations: A Global Meta-Epidemiological Study

The rs1801133 (C677T) polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene has been linked to type 2 diabetes (T2D) risk. This study aimed to assess the association between rs1801133 genotypes (CC, CT, TT) and T2D across multiethnic populations and to identify genotype- and region-specific risks. A global meta-epidemiological analysis was conducted using data from 19 studies comprising 6479 participants from Asia, Africa, Europe, and America. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses by region were also performed. The results of the CC vs. CT dominant genetic model were OR 95% CI = 0.63 (0.46–0.87); p = 0.005; the CC vs. TT genetic recessive model yielded OR 95% CI = 0.59 (0.38–0.91); p = 0.02; and the CT vs. TT codominance genetic model yielded OR 95% CI = 0.95 (0.65–1.37); p = 0.78. Based on the subgroup analysis, the CC genotype is predominantly associated with an increased risk of T2D in both Africa and Europe. From this study, the CC genotype was proven to be highly contributory to T2D risk compared to the CT and TT genotypes. These findings highlight the need for ethnicity-informed genetic screening and targeted prevention strategies in global diabetes management.