Mechanisms
ANGPTL3 abnormalities outnumber CETP abnormalities in Japanese hyperalphalipoproteinemic subjects (Clin Chim Acta 2008)
Original title: Higher frequency of abnormal serum angiopoietin-like protein 3 than abnormal cholesteryl ester transfer protein in Japanese hyperalphalipoproteinemic subjects
Researchers measured serum angiopoietin-like protein 3 (ANGPTL3) and CETP, both regulators of HDL cholesterol, in Japanese subjects grouped by HDL-C level: low (n=51, <40 mg/dL), normal (n=126, 40-90 mg/dL), and high (n=89, >90 mg/dL, hyperalphalipoproteinemic or HALT). Using the normal-HDL group to define reference ranges (ANGPTL3 218 +/- 144 ng/mL; CETP 1.29 +/- 0.90 ug/mL), abnormally high ANGPTL3 (>362 ng/mL) was far more frequent in HALT subjects (44%) than abnormally low CETP (<0.39 ug/mL, 4.5%). ANGPTL3 correlated strongly with HDL-C (r=0.67, P<0.0001) and adiponectin (r=0.57, P<0.0001), but CETP did not correlate with either. The authors conclude ANGPTL3, an inhibitor of endothelial lipase, may be more strongly linked to elevated HDL-C than CETP and could be a better target for modulating HDL-C.
Original abstract
Background: Either a decrease of cholesteryl ester transfer protein (CETP) or an increase of angiopoietin-like protein 3 (ANGPTL3) in plasma has been shown to increase HDL-cholesterol (HDL-C) levels. However, as yet, it is not known which protein is more strongly associated with the modulation of HDL in the Japanese hyperalphalipoproteinemic (HALT) subjects.
Methods: The serum concentration of ANGPTL3 and CETP, together with total cholesterol (TC), triglycerides (TG), adiponectin and ApoE phenotypes were determined in three groups with different HDL-C concentrations: low, <40 mg/dl (n=51); normal, 40-90 mg/dl (n=126) and high, >90 mg/dl (n=89) in the average Japanese population.
Results: The normal range (mean+/-2SD) of serum ANGPTL3 (218+/-144 ng/ml) and CETP (1.29+/-0.90 microg/ml) were determined in cases with 40-90 mg/dl HDL-C concentration. The frequency of abnormally high ANGPTL3 cases (>362 ng/ml) were found to be significantly greater (44%) compared with those of low CETP cases (<0.39 microg/ml, 4.5%) in HALT cases (>90 mg/dl). ANGPTL3 showed a high correlation with HDL-C (r=0.67, P<0.0001) and adiponectin (r=0.57, P<0.0001), but not with CETP.
Conclusion: In average Japanese population, abnormally higher frequency of increased ANGPTL3 prevail in HALT cases as compared with cases with low CETP. These findings suggest that ANGPTL3, the inhibitor of endothelial lipase, may be more strongly associated with increased HDL-C rather than CETP in plasma. Accordingly, ANGPTL3 seems to be a better target for the modulation of HDL-C.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.