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Lookup NU author(s): Dr Kate Potter,
Professor Anthony MoormanORCiD,
Professor Caroline Relton,
Professor John Mathers,
Dr Gordon Strathdee,
Dr Jill McKay
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley - V C H Verlag GmbH & Co. KGaA, 2018.
For re-use rights please refer to the publisher's terms and conditions.
Scope; Inadequate maternal folate intake is associated with increased childhood acute lymphoblastic leukaemia (ALL) risk. Folate provides methyl groups for DNA methylation, which is dramatically disrupted in ALL. We investigated if maternal folate (and related B-vitamin) intake during pregnancy may affect ALL risk via influencing DNA methylation. Methods and Results; We identified genes in which methylation changes were reported both in response to folate status and in ALL. Folate-responsive genes (n=526) were identified from mouse models of maternal folate depletion during pregnancy. Using published data, we identified 2621 genes with persistently altered methylation in ALL. Twenty-five overlapping genes were found, with the same directional methylation change in response to folate depletion and in ALL. We confirmed hypermethylation of a subset of genes (ASCL2, KCNA1, SH3GL3, SRD5A2) in ALL by measuring 20 patient samples using pyrosequencing. In a nested cohort of cord blood samples (n=148), SH3GL3 methylation was inversely related to maternal RBC folate concentrations (p=0.008). Furthermore, ASCL2 methylation was inversely related to infant vitamin B12 levels. (p=0.016). Conclusion; Findings demonstrate proof of concept for a plausible mechanism i.e. variation in DNA methylation, by which low intake of folate, and related B-vitamins during pregnancy may influence ALL risk.
Author(s): Potter C, Moorman AV, Relton CL, Ford D, Mathers JC, Strathdee G, McKay JA
Publication type: Article
Publication status: Published
Journal: Molecular Nutrition & Food Research
Print publication date: 01/11/2018
Online publication date: 07/09/2018
Acceptance date: 24/08/2018
Date deposited: 20/09/2018
ISSN (print): 1613-4125
ISSN (electronic): 1613-4133
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
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