CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials.
Study Goal
The researchers aimed to determine whether the CETP genetic variant rs3764261 modifies the effect of high-fat vs. low-fat weight-loss diets on changes in lipid levels.
Results Summary
Individuals with the CETP rs3764261 CC genotype on a high-fat diet showed greater increases in HDL cholesterol and decreases in triglycerides compared to those on a low-fat diet, with results replicated in an independent trial. No significant differences were observed among other genotypes.
Population
Overweight/obese adults (732 in the primary trial, 171 in the replication trial).
Effective Dosage
Not specified
Duration
2 years
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
high-fat diet | increase | HDL cholesterol | participants with the CETP rs3764261 CC genotype | - | larger increases | #1 |
high-fat diet | decrease | triglycerides | participants with the CETP rs3764261 CC genotype | - | decreases | #2 |
low-fat diet | no change | HDL cholesterol | participants carrying other genotypes | - | no significant difference | #3 |
low-fat diet | no change | triglycerides | participants carrying other genotypes | - | no significant difference | #4 |
low-carbohydrate/high-fat weight-loss diet | increase | HDL cholesterol | individuals with the CETP rs3764261 CC genotype | - | greater effects on raising | #5 |
low-carbohydrate/high-fat weight-loss diet | decrease | triglycerides | individuals with the CETP rs3764261 CC genotype | - | lowering | #6 |
Little is known about whether cholesteryl ester transfer protein (CETP) genetic variation may modify the effect of weight-loss diets varying in fat content on changes in lipid levels. We analyzed the interaction between the CETP variant rs3764261 and dietary interventions on changes in lipid levels among 732 overweight/obese adults from a 2 year randomized weight-loss trial [Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST)], and replicated the findings in 171 overweight/obese adults from an independent 2 year weight-loss trial [Dietary Intervention Randomized Controlled Trial (DIRECT)]. In the POUNDS LOST, participants with the CETP rs3764261 CC genotype on the high-fat diet had larger increases in HDL cholesterol (P = 0.001) and decreases in triglycerides (P = 0.007) than those on the low-fat diet at 6 months, while no significant difference between these two diets was observed among participants carrying other genotypes. The gene-diet interactions on changes in HDL-cholesterol and tri-glyc-erides were replicated in the DIRECT (pooled P for interaction ≤ 0.01). Similar results on trajectory of changes in HDL cholesterol and triglycerides over the 2 year intervention were observed in both trials. Our study provides replicable evidence that individuals with the CETP rs3764261 CC genotype might derive greater effects on raising HDL cholesterol and lowering triglycerides by choosing a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet.