Genetics
CETP genotype fails to predict LDL cholesterol response to dietary fat, contradicting earlier studies (Nutr Metab Cardiovasc Dis 2005)
Original title: Variation in the cholesteryl ester transfer protein (CETP) gene does not influence individual plasma cholesterol response to changes in the nature of dietary fat
In a crossover trial, 35 individuals with the CETP Taq1 B1B1 genotype were age- and sex-matched with individuals carrying one or two CETP B2 alleles, and both groups completed a four-week high-saturated-fat diet phase and a four-week high-polyunsaturated-fat diet phase with no washout between them. The difference in LDL-cholesterol between the PUFA and SAFA diets was 0.95 mmol/l (95% CI 0.71-1.19) in the B1B1 group versus 0.80 mmol/l (0.57-1.04) in the B2-carrier group, a non-significant difference (p=0.38); total cholesterol showed comparable results, and neither genotype group showed a significant HDL response to either diet. Response also did not differ by APOE or lipoprotein lipase genotype. The authors conclude CETP genotype does not significantly affect dietary-fat-induced changes in total and LDL cholesterol, contrary to some earlier reports.
Original abstract
Background And Aims: Some individuals respond to a greater extent than others to changes in dietary fat and cholesterol even when dietary intake is consistent. A prospective study has been undertaken in which two groups of individuals according to cholesteryl ester transfer protein (CETP) genotype were compared in terms of plasma lipid response to altering the nature of dietary fat in a free-living situation.
Methods And Results: Following genotyping, 35 individuals with the CETP Taq1 B1B1 genotype were paired with age and sex-matched individuals with one or two CETP B2 alleles, to undertake a single crossover trial with a diet high in saturated fat and a diet high in polyunsaturated fat. There was no washout period between the two 4-week phases. Plasma lipoproteins were measured at the beginning and end of each phase. The difference (95% CI) in plasma LDL-cholesterol concentration at the end of the PUFA and SAFA diets was 0.95 (0.71, 1.19) mmol/l in the CETP B1B1 group and 0.80 (0.57, 1.04) mmol/l in the group with at least one CETP B2 allele. The dietary induced changes in the two genotype groups were not significantly different (p=0.38) from each other. Comparable results were observed for plasma total cholesterol. The high PUFA and SAFA diets did not significantly alter plasma HDL concentration in either of the CETP genotype groups. Response was also similar according to apolipoprotein E genotype (E3E3 vs E4+) and lipoprotein lipase genotype (S447X).
Conclusions: The results of this study do not support previous studies in which CETP genotype predicted plasma LDL-cholesterol response to diet. CETP genotype does not significantly affect the change in plasma total and LDL-cholesterol concentrations that occur when altering the nature of dietary fat. These data suggest that the influence of genetic factors on total and LDL-cholesterol may be relatively small in comparison with the effect of dietary manipulation.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.