Show simple item record

dc.contributor.authorMOLLOY, ANNEen
dc.date.accessioned2011-08-29T10:44:33Z
dc.date.available2011-08-29T10:44:33Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationStone N, Pangilinan F, Molloy AM, Shane B, Scott JM, Ueland PM, Mills JL, Kirke PN, Sethupathy P, Brody LC, Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes., PloS One, 6, 7, 2011, e21851en
dc.identifier.issn1932-6203en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/59128
dc.descriptionPUBLISHEDen
dc.description.abstractOne-carbon metabolism (OCM) is linked to DNA synthesis and methylation, amino acid metabolism and cell proliferation. OCM dysfunction has been associated with increased risk for various diseases, including cancer and neural tube defects. MicroRNAs (miRNAs) are ~22 nt RNA regulators that have been implicated in a wide array of basic cellular processes, such as differentiation and metabolism. Accordingly, mis-regulation of miRNA expression and/or activity can underlie complex disease etiology. We examined the possibility of OCM regulation by miRNAs. Using computational miRNA target prediction methods and Monte-Carlo based statistical analyses, we identified two candidate miRNA ?master regulators? (miR-22 and miR-125) and one candidate pair of ?master co-regulators? (miR-344-5p/484 and miR-488) that may influence the expression of a significant number of genes involved in OCM. Interestingly, miR-22 and miR-125 are significantly up-regulated in cells grown under low-folate conditions. In a complementary analysis, we identified 15 single nucleotide polymorphisms (SNPs) that are located within predicted miRNA target sites in OCM genes. We genotyped these 15 SNPs in a population of healthy individuals (age 18?28, n = 2,506) that was previously phenotyped for various serum metabolites related to OCM. Prior to correction for multiple testing, we detected significant associations between TCblR rs9426 and methylmalonic acid (p = 0.045), total homocysteine levels (tHcy) (p = 0.033), serum B12 (p < 0.0001), holo transcobalamin (p < 0.0001) and total transcobalamin (p < 0.0001); and between MTHFR rs1537514 and red blood cell folate (p < 0.0001). However, upon further genetic analysis, we determined that in each case, a linked missense SNP is the more likely causative variant. Nonetheless, our Monte-Carlo based in silico simulations suggest that miRNAs could play an important role in the regulation of OCM.en
dc.description.sponsorshipThis study was supported by the Intramural Research Programs of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Human Genome Research Institute.en
dc.format.extente21851en
dc.language.isoenen
dc.relation.ispartofseriesPloS Oneen
dc.relation.ispartofseries6en
dc.relation.ispartofseries7en
dc.rightsYen
dc.subjectGeneticsen
dc.subjectBiochemistryen
dc.subjectMicroRNAen
dc.titleBioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/amolloyen
dc.identifier.rssinternalid74752en
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0021851en
dc.subject.TCDThemeGenes & Societyen
dc.identifier.rssurihttp://dx.doi.org/10.1371/journal.pone.0021851en
dc.identifier.orcid_id0000-0002-1688-9049en


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record