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

Maria G. Kakkoura, Kleitos Sokratous, Christiana A. Demetriou, Maria A. Loizidou, Giorgos Loucaides, Eleni Kakouri, Andreas Hadjisavvas, Kyriacos Kyriacou

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1600558
JournalMolecular Nutrition and Food Research
Issue number4
Publication statusPublished - 1 Apr 2017


  • Mediterranean dietary pattern
  • Nutrigenetics
  • One-carbon metabolism
  • Serum-targeted metabolomics
  • Xenobiotic metabolism


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