Changes in triglyceride-rich lipoprotein particle profiles in response to 1 week on a low fat or Mediterranean diet by TCF7L2 rs7903146 genotype: A randomized crossover dietary intervention trial

Authors: Lai, Chao Qiang; GERVIS, JULIE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Parnell, Laurence; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Genes and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/19/2025
Publication Date: 3/6/2025
Citation: Lai, C., Gervis, J.E., Parnell, L.D., Lichtenstein, A.H., Ordovas, J.M. 2025. Changes in triglyceride-rich lipoprotein particle profiles in response to 1 week on a low fat or Mediterranean diet by TCF7L2 rs7903146 genotype: A randomized crossover dietary intervention trial. Genes and Nutrition. 20. Article 4. https://doi.org/10.1186/s12263-025-00763-y.
DOI: https://doi.org/10.1186/s12263-025-00763-y

Interpretive Summary: Heart problems and metabolic issues are a big worry for many people. Our genes, like the TCF7L2 gene, can make us more susceptible to these problems. ARS and Tufts scientists at JM-USDA Human Nutrition Research Center on Aging have found that what you eat may change the way this gene works. They studied two diets: one low-fat diet and one Mediterranean diet. They found that a diet rich in Mediterranean foods, like olive oil and nuts, was better for keeping blood healthy, especially for people with the TT version of the TCF7L2 gene. So, if you have this version of the gene, eating Mediterranean foods may keep your heart strong. This means that eating the right foods for our genes can help us keep our hearts healthy.

Technical Abstract: Background & aims: TCF7L2 is one of the most common genetic factors responsible for metabolic and cardiovascular disease (CVD) risk. We previously found that subjects with the TT genotype who consuming a low-fat diet (LF) had a higher incidence of stroke than subjects with the CC genotype, whereas this association was abolished in subjects with the TT genotype who consumed a Mediterranean-type diet (MetD). However, the mechanism by which MetD diet modulates the association between TCF7L2 and CVD risk is unclear. This study aims to validate these findings under real-world conditions and clinical practice to elucidate the biological mechanisms involved in this correlation. Methods: Thirty-five participants were recruited based on rs7903146 genotype. Of those consented to participate, 21 had the CC and 14 had the TT genotype. Participants were randomized into two dietary intervention groups with equal ratio of CC and TT carriers. Each participants followed one of two diets (LF or MetD) for one week, followed by a one week washout period before switching to the other diet for one week. Blood samples were collected before and after each diet for metabolomic analysis using nuclear magnetic resonance (NMR) spectroscopy. The differential effect of the diets on triglyceride-rich lipoproteins was determined based on TCF7L2 genotype. Results: The MetD reduced triglyceride-rich lipoprotein concentrations significantly more than the LF diet. After consuming the LF diet, TT carriers exhibited more small VLDL particles, potentially contributing to CVD rsik compared to the CC carriers. However, this difference in risk was not observed with the MetD. Furthermore, the order in which the two diets were crossed affected the triglyceride-rich lipoprotein profile, with LF-MetD regimen showing a stronger effect on TRL levels than the than MetD-LF regimen. Conclusions: Our findings suggest that rs7903146 TT carriers benefit more from a MetD than a LF diet in terms of their triglyceriderich lipoprotein profile, which may reduce their risk of CVD. These results support the notion that genotype is a factor in determining the extent to which the MetD affects cardiovascular health.