title: CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials.
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.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY; Departments of Nutrition Harvard School of Public Health, Boston, MA.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Cardiology Department Hadassah Hebrew University Medical Center, Jerusalem, Israel; Center for Research, Prevention, and Treatment of Atherosclerosis Internal Medicine Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Durst
authors.affiliation: Nuclear Research Center, Dimona, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Schwarzfuchs
authors.affiliation: Center for Research, Prevention, and Treatment of Atherosclerosis Internal Medicine Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Leitersdorf
authors.affiliation: Center for Research, Prevention, and Treatment of Atherosclerosis Internal Medicine Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Shoshi
authors.initials: S
authors.lastname: Shpitzen
authors.affiliation: Departments of Nutrition Harvard School of Public Health, Boston, MA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Departments of Nutrition Harvard School of Public Health, Boston, MA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Champagne
authors.affiliation: Departments of Nutrition Harvard School of Public Health, Boston, MA; Epidemiology, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Departments of Nutrition Harvard School of Public Health, Boston, MA; Epidemiology, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.affiliation: Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA.
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.affiliation: Departments of Nutrition Harvard School of Public Health, Boston, MA.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
authors.affiliation: Department of Public Health, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Shai
authors.affiliation: Departments of Nutrition Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Electronic address: nhlqi@channing.harvard.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D000328:Adult; D000368:Aged; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000235:genetics; D014280:Triglycerides / Q000097:blood*; D015431:Weight Loss
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004041:Dietary Fats; D014280:Triglycerides
keywords: Dietary Intervention Randomized Controlled Trial; Preventing Overweight Using Novel Dietary Strategies; cholesteryl ester transfer protein; gene-diet interaction