Background: DNA methylation has been linked to the development and progression of multiple disorders including T2D. One significant enzyme involved in DNA methylation is methylene tetrahydrofolate reductase (MTHFR). This study was designed to evaluate the association between rs1801133 and rs1801131 polymorphisms, located in the MTHFR, and T2D in an Iranian population.

Methods: Blood samples from 151 patients with T2D and 136 healthy individuals were collected and DNA was extracted using the salting out method. Variants were genotyped using amplification tetra-refractory mutation system-polymerase chain reaction analysis. The data were analyzed via independent sample t-test and x² tests.

Results: The rs1801131 A/C polymorphism significantly increased the risk of T2D in codominant heterozygous AC (P=0.008), homozygous CC (P=0.01), and recessive CC (P=0.001) genotypes. Significant correlations were found regarding rs1801133 T/C gene polymorphism and the risk of T2D in codominant heterozygous TC (P=0.001), homozygote CC (P=0.001), and recessive CC (P=0.0001) models. The presence of the C allele is a potential risk factor for T2D for rs1801133 T/C (P=0.001) and rs1801131 A/C (P=0.04) polymorphisms.

Conclusions: Both the rs1801133 T/C and rs1801131 A/C MTHFR polymorphisms significantly increased the risk of T2D in our population. Further studies in other ethnicities are necessary to verify our findings.