CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials

Qibin Qi, Ronen Durst, Dan Schwarzfuchs, Eran Leitersdorf, Shoshi Shpitzen, Yanping Li, Hongyu Wu, Catherine M. Champagne, Frank B. Hu, Meir J. Stampfer, George A. Bray, Frank M. Sacks, Iris Shai, Lu Qi

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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 triglycerides 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.

Original languageEnglish (US)
Pages (from-to)713-721
Number of pages9
JournalJournal of Lipid Research
Issue number3
StatePublished - Mar 1 2015


  • Cholesteryl ester transfer protein
  • Dietary intervention randomized controlled trial
  • Gene-diet interaction
  • Preventing overweight using novel dietary strategies

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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