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

Martina Rooney, T Bottiglieri, B Wasek-Patterson, A McMahon, Catherine F. Hughes, A McCann, G Horigan, J.J. Strain, H McNulty, M Ward

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)91-99
Number of pages9
JournalBiochimie
Volume173
Early online date21 Apr 2020
DOIs
Publication statusPublished - 30 Jun 2020

Keywords

  • MTHFR
  • Riboflavin
  • S-adenosylmethionine
  • One-Carbon Metabolism
  • Hypertension
  • One-carbon metabolism

Fingerprint Dive into the research topics of 'Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation'. Together they form a unique fingerprint.

  • Profiles

    No photo of Mary Ward

    Mary Ward

    Person: Academic

    Cite this