Mediterranean diet-gene interactions: A targeted metabolomics study in Greek-Cypriot women

Mol Nutr Food Res. 2017 Apr;61(4). doi: 10.1002/mnfr.201600558. Epub 2017 Jan 25.

Abstract

Scope: A high adherence to the Mediterranean diet (MD) was previously associated with a decreased risk of breast cancer (BC) among Greek-Cypriot women. Additionally, particular polymorphisms were shown to modulate this MD-BC association. Herein, we aimed to investigate the effect of polymorphisms-MD interactions on the levels of specific metabolites that could be related to dietary adherence or enzymatic activity, which is itself modulated by polymorphisms.

Methods and results: Greek-Cypriot women who were BC controls and had the lowest or the highest MD adherence (vegetables, fruit, legumes, fish) as assessed by principal component analysis (n = 564) were included. Participants were previously genotyped for nine polymorphisms of the one-carbon metabolism, oxidative stress, and xenobiotic metabolism. The serum levels of 14 metabolites that are key players in the aforementioned pathways were measured by UPLC-MS/MS. ANCOVA was used to assess polymorphism-MD interactions on metabolites' levels within a multivariate linear regression model. Statistically significant interactions between GSTM1 (where GST is glutathione S-transferase) deletion polymorphism and MD on flavin mononucleotide and on 5-methyltetrahydrofolate (5-MTHF) concentrations were observed. The MTHFR rs1801133 interacted significantly with MD on 5-MTHF concentration.

Conclusion: Serum levels of flavin mononucleotide and 5-MTHF were shown to be influenced by interactions between GSTM1 deletion or MTHFR (rs1801133) polymorphisms and a dietary pattern, characteristic of MD.

Keywords: Mediterranean dietary pattern; Nutrigenetics; One-carbon metabolism; Serum-targeted metabolomics; Xenobiotic metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diet therapy*
  • Diet, Mediterranean*
  • Fabaceae
  • Female
  • Fruit
  • Genotype
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Greece
  • Humans
  • Metabolomics*
  • Middle Aged
  • Oxidative Stress
  • Polymorphism, Genetic
  • Tetrahydrofolates
  • Vegetables

Substances

  • Tetrahydrofolates
  • Glutathione Transferase
  • 5-methyltetrahydrofolate