Dilip K Yadav1, Smeeta Shrestha1,2, Karen A Lillycrop3, Charu V Joglekar4, Hong Pan5, Joanna D Holbrook5,6, Caroline Hd Fall7, Chittaranjan S Yajnik4, Giriraj R Chandak1,8. 1. Genomic Research on Complex Diseases (GRC Group), CSIR-Centre for Cellular & Molecular Biology, Hyderabad, Telangana, 500 007, India. 2. Building No 7, School of Basic & Applied Sciences, Dayananda Sagar University, Shavige Malleshwara Hills, Kumaraswamy Layout, Bangalore 560 078, Karnataka, India. 3. Research Centre for Biological Sciences, Institute of Developmental Sciences, Southampton General Hospital, Southampton, SO16 6 YD, UK. 4. Diabetes Unit, King Edward Memorial Hospital & Research Centre, Rasta Peth, Pune, Maharashtra, 411 011, India. 5. Singapore Institute for Clinical Sciences, A*STAR, Brenner Centre for Molecular Medicine, 30 Medical Drive, 119521, Singapore. 6. Human Development & Health Academic Unit, University of Southampton & National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6 YD, UK. 7. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, SO16 6 YD, UK. 8. Adjunct Faculty, Human Genetics Unit, Genome Institute of Singapore, Biopolis, 138672, Singapore.
Abstract
AIM: To investigate the effect of B12 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 B12 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 B12 (589 differentially methylated CpGs and 2892 regions) and B12 + 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 B12-supplementation cohort. We also demonstrate that methylation influences miR21 expression and FTO, TCF7L2, CREBBP/CBP and SIRT1 are direct targets of miR21-3p. CONCLUSION: B12 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.
AIM: To investigate the effect of B12 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 B12 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 B12 (589 differentially methylated CpGs and 2892 regions) and B12 + 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 B12-supplementation cohort. We also demonstrate that methylation influences miR21 expression and FTO, TCF7L2, CREBBP/CBP and SIRT1 are direct targets of miR21-3p. CONCLUSION: B12 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.
Entities:
Keywords:
Type 2 diabetes; folic acid; miRNAs; molecular mechanisms; supplementation; vitamin B12; DNA methylation
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