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

doi:10.1194/jlr.p055715

Abstract

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.

Highlights

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
In the current study, we examined whether the CETP rs3764261 genotype modulated changes in lipid levels in response to weight-loss diets varying in fat content in a 2 year randomized intervention study: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) [28]
Consistent with the overall POUNDS LOST [28] and Dietary Intervention Randomized Controlled Trial (DIRECT) [29] trial results, the reported dietary intakes confirmed that participants modified their intake of macronutrients in the direction of the intervention (Table 2)

Summary

Introduction

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. In patients with low Abbreviations: CETP, cholesteryl ester transfer protein; DIRECT, Dietary Intervention Randomized Controlled Trial; GWAS, genomewide association study; POUNDS LOST, Preventing Overweight Using Novel Dietary Strategies. Several observational studies reported that CETP variants might interact with dietary factors, especially dietary fat intake, on HDL cholesterol levels [12,13,14,15], the findings were not consistently replicated [11, 16,17,18,19,20]. In the current study, we examined whether the CETP rs3764261 genotype modulated changes in lipid levels in response to weight-loss diets varying in fat content in a 2 year randomized intervention study: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) [28]. We replicated our findings in an independent 2 year intervention study: the Dietary Intervention Randomized Controlled Trial (DIRECT) [29]

Methods

Results

Conclusion