Vitamin B12 supplementation influences methylation of genes associated with Type 2 diabetes and its intermediate traits

Aim: To investigate the effect of B-12 and/or folic acid supplementation on genome-wide DNA methylation. Methods: We performed Infinium HumanMethylation450 BeadChip (Zymo Research, CA, USA) assay in children supplemented with B-12 and/or folic acid (n = 12 in each group) and investigated the functional mechanism of selected differentially methylated loci. Results: We noted significant methylation changes postsupplementation in B-12 (589 differentially methylated CpGs and 2892 regions) and B-12 + folic acid (169 differentially methylated CpGs and 3241 regions) groups. Type 2 diabetes-associated genes TCF7L2 and FTO; and a miRNA, miR21 were further investigated in another B-12-supplementation cohort. We also demonstrate that methylation influences miR21 expression and FTO, TCF7L2, CREBBP/CBP and SIRT1 are direct targets of miR21-3p. Conclusion: B-12 supplementation influences regulation of several metabolically important Type 2 diabetes-associated genes through methylation of miR21. Hence, our study provides novel epigenetic explanation for the association between disordered one carbon metabolism and risk of adiposity, insulin resistance and diabetes and has translational potential.