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Impact of the MTHFR C677T polymorphism on one-carbon metabolites: evidence from a randomised trial of riboflavin supplementation.

Rooney, Martina; Bottiglieri, Teodoro; Wasek-Patterson, Brandi; McMahon, Amy; Hughes, Catherine F.; McCann, Adrian; Horigan, Geraldine; Strain, J.J.; McNulty, Helene; Ward, Mary

Authors

Teodoro Bottiglieri

Brandi Wasek-Patterson

Amy McMahon

Catherine F. Hughes

Adrian McCann

Geraldine Horigan

J.J. Strain

Helene McNulty

Mary Ward



Abstract

Homozygosity for the C677T polymorphism in MTHFR (TT genotype) is associated with a 24–87% increased risk of hypertension. Blood pressure (BP) lowering was previously reported in adults with the TT genotype, in response to supplementation with the MTHFR cofactor, riboflavin. Whether the BP phenotype associated with the polymorphism is related to perturbed one-carbon metabolism is unknown. This study investigated one-carbon metabolites and their responsiveness to riboflavin in adults with the TT genotype. Plasma samples from adults (n 115) screened for the MTHFR genotype, who previously participated in RCTs to lower BP, were analysed for methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline and cystathionine by liquid chromatography tandem mass spectrometry (LC-MS/MS). The one-carbon metabolite response to riboflavin (1.6 mg/d; n 24) or placebo (n 23) for 16 weeks in adults with the TT genotype was also investigated. Plasma SAM (74.7 ± 21.0 vs 85.2 ± 22.6 nmol/L, P = 0.013) and SAM:SAH ratio (1.66 ± 0.55 vs 1.85 ± 0.51, P = 0.043) were lower and plasma homocysteine was higher (P = 0.043) in TT, compared to CC individuals. In response to riboflavin, SAM (P = 0.008) and cystathionine (P = 0.045) concentrations increased, with no responses in other one-carbon metabolites observed. These findings confirm perturbed one-carbon metabolism in individuals with the MTHFR 677TT genotype, and for the first time demonstrate that SAM, and cystathionine, increase in response to riboflavin supplementation in this genotype group. The genotype-specific, one-carbon metabolite responses to riboflavin intervention observed could offer some insight into the role of this gene-nutrient interaction in blood pressure.

Citation

ROONEY, M., BOTTIGLIERI, T., WASEK-PATTERSON, B., MCMAHON, A., HUGHES, C.F., MCCANN, A., HORIGAN, G., STRAIN, J.J., MCNULTY, H. and WARD, M. 2020. Impact of the MTHFR C677T polymorphism on one-carbon metabolites: evidence from a randomised trial of riboflavin supplementation. Biochimie [online], 173, pages 91-99. Available from: https://doi.org/10.1016/j.biochi.2020.04.004

Journal Article Type Article
Acceptance Date Apr 6, 2020
Online Publication Date Apr 21, 2020
Publication Date Jun 30, 2020
Deposit Date Sep 3, 2021
Publicly Available Date Sep 3, 2021
Journal Biochimie
Print ISSN 0300-9084
Electronic ISSN 6183-1638
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 173
Pages 91-99
DOI https://doi.org/10.1016/j.biochi.2020.04.004
Keywords MTHFR; Riboflavin; S-adenosylmethionine; One-carbon metabolism; Hypertension
Public URL https://rgu-repository.worktribe.com/output/1437281

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