Genetics
CETP deficiency, not high CETP activity, impairs postprandial lipemia clearance and correlates with carotid atherosclerosis in women (Lipids Health Dis 2011)
Original title: A reduction of CETP activity, not an increase, is associated with modestly impaired postprandial lipemia and increased HDL-cholesterol in adult asymptomatic women
Classifying twenty-eight asymptomatic women from a healthy sample of 148 into CETP deficiency (n=8), high CETP activity (n=6), and control (n=14) groups, and giving each an oral fat tolerance test, researchers found CETP-deficient women had higher HDL and apoA-I concentrations but delayed postprandial lipemia clearance, evidenced by modified triglyceride-rich-lipoprotein clearance parameters. No genetic determinants of CETP deficiency or postprandial lipemia were identified. Within the CETP-deficient group, postprandial parameters correlated with carotid intima-media thickness in a pro-atherogenic direction, and multivariate regression showed CETP activity was strongly and negatively predicted by postprandial VLDL-cholesterol increase (R2=92%) and itself negatively regulated the postprandial rise in apoB-100-containing lipoproteins (R2=85%), suggesting moderate CETP deficiency produces paradoxically high HDL-C alongside atherogenic postprandial lipemia.
Original abstract
Background: The relationship between CETP and postprandial hyperlipemia is still unclear. We verified the effects of varying activities of plasma CETP on postprandial lipemia and precocious atherosclerosis in asymptomatic adult women.
Methods: Twenty-eight women, selected from a healthy population sample (n = 148) were classified according to three CETP levels, all statistically different: CETP deficiency (CETPd ≤ 4.5%, n = 8), high activity (CETPi ≥ 23.8, n = 6) and controls (CTL, CETP ≥ 4.6% and ≤ 23.7%, n = 14). After a 12 h fast they underwent an oral fat tolerance test (40 g of fat/m² of body surface area) for 8 hours. TG, TG-rich-lipoproteins (TRL), cholesterol and TRL-TG measurements (AUC, AUIC, AR, RR and late peaks) and comparisons were performed on all time points. Lipases and phospholipids transfer protein (PLTP) were determined. Correlation between carotid atherosclerosis (c-IMT) and postprandial parameters was determined. CETP TaqIB and I405V and ApoE-ε3/ε2/ε4 polymorphisms were examined. To elucidate the regulation of increased lipemia in CETPd a multiple linear regression analysis was performed.
Results: In the CETPi and CTL groups, CETP activity was respectively 9 and 5.3 higher compared to the CETPd group. Concentrations of all HDL fractions and ApoA-I were higher in the CETPd group and clearance was delayed, as demonstrated by modified lipemia parameters (AUC, AUIC, RR, AR and late peaks and meal response patterns). LPL or HL deficiencies were not observed. No genetic determinants of CETP deficiency or of postprandial lipemia were found. Correlations with c-IMT in the CETPd group indicated postprandial pro-atherogenic associations. In CETPd the regression multivariate analysis (model A) showed that CETP was largely and negatively predicted by VLDL-C lipemia (R² = 92%) and much less by TG, LDL-C, ApoAI, phospholipids and non-HDL-C. CETP (model B) influenced mainly the increment in ApoB-100 containing lipoproteins (R² = 85% negatively) and phospholipids (R² = 13%), at the 6(th)h point.
Conclusion: The moderate CETP deficiency phenotype included a paradoxically high HDL-C and its sub fractions (as earlier described), positive associations with c-IMT, a postprandial VLDL-C increment predicting negatively CETP activity and CETP activity regulating inversely the increment in ApoB100-containing lipoproteins. We hypothesize that the enrichment of TG content in triglyceride-rich ApoB-containing lipoproteins and in TG rich remnants increases lipoproteins' competition to active lipolysis sites,reducing their catabolism and resulting on postprandial lipemia with atherogenic consequences.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.