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Maternal red blood cell folate and infant vitamin B12 status influence methylation of genes associated with childhood acute lymphoblastic leukaemia

Lookup NU author(s): Dr Kate Potter, Professor Anthony MoormanORCiD, Professor Caroline Relton, Professor John Mathers, Dr Gordon Strathdee, Dr Jill McKay

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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.

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Abstract

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.

Publication metadata

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

Year: 2018

Volume: 62

Issue: 22

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

URL: https://doi.org/10.1002/mnfr.201800411

DOI: 10.1002/mnfr.201800411

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