Specifically, we applied a computational strategy to predict whether any known human miRNAs are candidate regulators of the genes most commonly associated with OCM. In a complementary analysis, we also assessed whether genetic variants within predicted miRNA target sites in OCM genes are associated with relevant metabolites. In this study we describe a computational strategy for the identification of candidate master miRNA regulators of a group of 42 OCM-related genes. Based on our target prediction analyses with the most stringent conservation criteria, we discover a novel role for miR-22 as a candidate master regulator of OCM. miR-22 is widely expressed and has been previously linked to cancer. Vitamin B12 transport via TCblR and TCN2 influences SAM production by regulating the activity of the B12- dependent MTR enzyme. Folate is required for this process and is transported from the circulation into cells by the reduced folate carrier, the product of the SLC19A1 gene. Finally, MTHFD2 is important for the exchange of one-carbon units between the cytoplasm and the mitochondrion. Coordinated regulation of these genes by miR-22 is likely to influence OCM and downstream epigenetic processes. Our results revealed another potential master regulator of OCM, miR-125/351. The large majority of its predicted targets are conserved only in primates, indicating that its putative role in regulating OCM may be more evolutionarily recent. It also appears likely that while miR-125/351 functions cooperatively with other miRNAs to impose regulation on OCM genes, miR229s influence in OCM may have evolved independently from other miRNAs. Notably, both miR-22 and miR-125/351 significantly increase in expression upon folate deficiency, lending further support to the prediction that these two miRNAs are relevant to folate-mediated OCM. Our results suggest that VE-821 miR-344-5p/484 and miR-488 may act in a cooperative fashion to regulate OCM. Neither miR-344-5p/484 nor miR-488 was included in the Marsit et al. study that examined miRNA expression under folate-deficient conditions. Future investigations, including loss-of-function experiments using antagomirs or “sponge�?constructs are required to validate the predicted role of miR-22, miR-125/351, miR-344-5p/484 and miR-488 as important regulators of OCM genes. In a complementary, independent experiment, we genotyped 17 SNPs located within predicted miRNA target sites in OCM genes and found significant associations between two of the SNPs and several metabolites. However, further analyses suggested that these associations could be accounted for by nearby functional variants that are in strong linkage disequilibrium with the miRNA target site SNPs. Nonetheless, we believe that our approach, which combines bioinformatic and genetic experiments, provides a useful model for exploring the role of miRNAs in basic physiological processes.