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

Vitamin B12 supplementation influences methylation of genes associated with Type 2 diabetes and its intermediate traits
Vitamin B12 supplementation influences methylation of genes associated with Type 2 diabetes and its intermediate traits
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.
1750-1911
71-90
Yadav, Dilip K.
eedf8cb6-a5d1-486f-aeab-140ef6e731fa
Shrestha, Smeeta
a1317ac1-6da8-4f72-8ae0-770f5ab253a3
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Joglekar, Charu V.
df226caf-a959-4047-8eb5-742b8381ac7f
Pan, Hong
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Holbrook, Joanna D.
69989b79-2710-4f12-946e-c6214e1b6513
Fall, Caroline H.D.
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Yajnik, Chittaranjan S.
f5777038-bba7-49bd-80b9-be4e586eecf4
Chandak, Giriraj R.
d9d4d4ba-6a4b-450d-8889-02e599ca0e1c
Yadav, Dilip K.
eedf8cb6-a5d1-486f-aeab-140ef6e731fa
Shrestha, Smeeta
a1317ac1-6da8-4f72-8ae0-770f5ab253a3
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Joglekar, Charu V.
df226caf-a959-4047-8eb5-742b8381ac7f
Pan, Hong
89ffb703-039c-4adc-9de9-1a125d3b2cf1
Holbrook, Joanna D.
69989b79-2710-4f12-946e-c6214e1b6513
Fall, Caroline H.D.
7171a105-34f5-4131-89d7-1aa639893b18
Yajnik, Chittaranjan S.
f5777038-bba7-49bd-80b9-be4e586eecf4
Chandak, Giriraj R.
d9d4d4ba-6a4b-450d-8889-02e599ca0e1c

Yadav, Dilip K., Shrestha, Smeeta, Lillycrop, Karen A., Joglekar, Charu V., Pan, Hong, Holbrook, Joanna D., Fall, Caroline H.D., Yajnik, Chittaranjan S. and Chandak, Giriraj R. (2018) Vitamin B12 supplementation influences methylation of genes associated with Type 2 diabetes and its intermediate traits. Epigenomics, 10 (1), 71-90. (doi:10.2217/epi-2017-0102).

Record type: Article

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.

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Yadav et al Epigenomics 2017 fina accepted version - Accepted Manuscript
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Accepted/In Press date: 20 October 2017
e-pub ahead of print date: 14 November 2017
Published date: 1 January 2018

Identifiers

Local EPrints ID: 416597
URI: https://eprints.soton.ac.uk/id/eprint/416597
ISSN: 1750-1911
PURE UUID: dfa795d0-dafe-4153-a24a-2c4f4e21ab18
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Joanna D. Holbrook: ORCID iD orcid.org/0000-0003-1791-6894

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Date deposited: 03 Jan 2018 17:30
Last modified: 09 Dec 2019 18:28

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Contributors

Author: Dilip K. Yadav
Author: Smeeta Shrestha
Author: Charu V. Joglekar
Author: Hong Pan
Author: Chittaranjan S. Yajnik
Author: Giriraj R. Chandak

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