Background: Cholesterol ester transfer protein (CETP) plays a key role in the transport of cholesteryl esters and triglycerides between the lipoproteins; and genetic variation in CETP gene has been related to blood lipids levels. It remains unclear whether CETP genetic variation may modulate effects of dietary intervention on lipid profiles.
Methods: We genotyped a CETP genetic variant rs3764261, which showed the strongest association with HDL cholesterol levels in previous GWAS, in the Pounds Lost trial and replicated in the DIRECT cohort. We compared the effects of high and low fat diets on changes in HDL cholesterol and triglycerides according to the genotypes of rs3764261.
Results: A significant interactions between the genotype and diet intervention on changes in HDL cholesterol (P for interaction =0.05) and triglycerides (P for interaction =0.002) was found. Among participants with CC genotype, the high-fat diet had greater effects on increases in HDL cholesterol (P=0.001) and decrease 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. 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, respectively) and triglycerides levels (P=0.06 and 0.003, respectively) than the low-fat diet among participants with CC genotype over the 2-year intervention in both trials.
Conclusions: Our data from two independent dietary intervention trials suggest that 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.
