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Background <p>The <i>TCF7L2</i> gene is a significant genetic factor contributing to the risk of metabolic and cardiovascular diseases (CVD). We previously found that subjects with the TT genotype of <i>TCF7L2</i> rs7903146 variant, who consume a low-fat diet (LF) had a higher incidence of stroke than subjects with the CC genotype. Yet 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 <i>TCF7L2</i> 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.</p> Methods <p>Thirty-five participants with BMI ranging from 27 to 34&#xa0;kg/m<sup>2</sup> were recruited based on rs7903146 genotype. Of those consented to participate, 21 had the CC and 14 had the TT genotype. Participants were randomly assigned to two dietary intervention groups, ensuring an equal distribution of CC and TT carriers. Each participant followed one of two diets (LF or MetD) for one week, followed by a 10-day 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 <i>TCF7L2</i> genotype.</p> Results <p>The MetD significantly reduced triglyceride-rich lipoprotein concentrations compared to the LF diet. After consuming the LF diet, TT carriers exhibited more small VLDL particles, potentially contributing to CVD risk compared to 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 triglyceride-rich lipoproteins (TRL) levels than the MetD-LF regimen.</p> Conclusions <p>Our findings suggest that rs7903146 TT carriers benefit more from a MetD than a LF diet in terms of their triglyceride-rich 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.</p>

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

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  • 发表日期：

    2025年3月6日

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  • Chao-Qiang Lai,
  • Julie E. Gervis,
  • Laurence D. Parnell,
  • Alice H. Lichtenstein,
  • Jose M. Ordovas

摘要

Background

The TCF7L2 gene is a significant genetic factor contributing to the risk of metabolic and cardiovascular diseases (CVD). We previously found that subjects with the TT genotype of TCF7L2 rs7903146 variant, who consume a low-fat diet (LF) had a higher incidence of stroke than subjects with the CC genotype. Yet 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 with BMI ranging from 27 to 34 kg/m2 were recruited based on rs7903146 genotype. Of those consented to participate, 21 had the CC and 14 had the TT genotype. Participants were randomly assigned to two dietary intervention groups, ensuring an equal distribution of CC and TT carriers. Each participant followed one of two diets (LF or MetD) for one week, followed by a 10-day 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 significantly reduced triglyceride-rich lipoprotein concentrations compared to the LF diet. After consuming the LF diet, TT carriers exhibited more small VLDL particles, potentially contributing to CVD risk compared to 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 triglyceride-rich lipoproteins (TRL) levels than the MetD-LF regimen.

Conclusions

Our findings suggest that rs7903146 TT carriers benefit more from a MetD than a LF diet in terms of their triglyceride-rich 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.