Background & aims: The current study aimed to systematically review the existing literature that investigated the modifying effect of genes on the relationship between dietary determinants and Metabolic syndrome (MetS).
Methods: A comprehensive search was performed on PubMed, Scopus, and Web of Science from inception to July 17, 2025, without any language restrictions, as long as the abstract was in English. The key keywords used were Diet, Nutrition, genetic factors, single-nucleotide polymorphisms (SNPs), and MetS.
Results: The literature included 40 observational studies. A significant interaction was identified between high intake of fat and genetic variations related to lipid metabolism, such as VEGF rs6921438 SNP, Caveolin-1 (CAV-1) rs3807992 SNP, Melanocortin-4 receptor (MC4R) rs12970134 SNP, Acetyl-CoA carboxylase (ACC2) rs4766587 SNP, PDZ domain containing 1 (PDZK1) i33968 SNP, ApoB rs512535 SNP, ApoA1 rs670 SNP, zinc transporters 8 (ZNT8) rs13266634 SNP, and circadian locomotor output cycles kaput (CLOCK) rs1801260 SNP. This interaction heightened the risk of MetS in individuals who are genetically predisposed to it. No interaction was found between alcohol consumption and the genotypes of alcohol dehydrogenase and aldehyde dehydrogenase. There are very few studies that have investigated the interaction between genes and macronutrients, micronutrients, food groups, and dietary patterns, and the results are inconsistent.
Conclusions: Due to the limited research in the nutrigenetics approach, the specific gene-nutrient interactions on MetS are not completely understood. Nevertheless, the results indicate that a high-fat diet interacts with certain genetic variations, particularly those involved in regulating lipid metabolism. This interaction is associated with an increased risk of MetS in individuals who are genetically predisposed.
Keywords: Diet; Gene; Interaction; Metabolic syndrome; SNP.
© 2025. The Author(s).