Abstract MP33: CETP Genetic Variation Modulates Effects of Weight-loss Diets on Lipid Profile in Two Independent 2-year Diet Intervention Studies: The Pounds Lost and Direct Trails
Background Cholesterol ester transfer protein (CETP) plays a key role in the transport of cholesteryl esters and triglycerides between the lipoproteins. It remains unclear whether CETP genetic variation may modulate effects of dietary intervention on lipid profile.
Methods We genotyped a CETP genetic variant rs3764261, which showed the strongest association with HDL cholesterol levels in previous GWAS, in 732 overweight adults from the Pounds Lost trial. We compared the effects of the high and low fat diets on changes in HDL cholesterol and triglycerides according to the genotypes of rs3764261. We replicated findings in 171 participants from the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT).
Results At baseline, the C allele of rs3764261 was significantly associated with low HDL cholesterol levels in participants from both trials. In the Pounds Lost, we found significant interactions between the genotype and diet intervention on changes in HDL cholesterol (P=0.05) and triglycerides (P=0.002). Among participants with CC genotype, the high-fat diet caused larger increases in HDL cholesterol (P=0.001) and decreases in triglycerides (P=0.007) than the low-fat diet at 6 months, while no significant difference between the 2 diet groups was observed among participants with CA/AA genotype. The findings were replicated in the DIRECT, in which the high-fat diet had greater effects on changes in HDL cholesterol and triglycerides than the low-fat diet among participants with CC genotype at 6 months (P≤0.0005; Figure). Generalized estimating equation analysis further indicated that the high-fat diet was more effective in improvement of HDL cholesterol (P=0.007 and 0.0001 in the Pounds Lost and DIRECT) and triglycerides (P=0.06 and 0.003) than the low-fat diet among participants with CC genotype over the 2-year intervention.
Conclusions Individuals with the CETP rs3764261 CC genotype might obtain more benefits in improvement of lipid profile by choosing a high-fat weight-loss diet compared with a low-fat diet.
- © 2013 by American Heart Association, Inc.