Genetics
Rare CETP-deficient case reveals independent control of remnant triglyceride and cholesterol after a fat load (Ann Clin Biochem 2009)
Original title: A deficiency of cholesteryl ester transfer protein whose serum remnant-like particle-triglyceride significantly increased, but serum remnant-like particle-cholesterol did not after an oral fat load
A 40-year-old man with compound heterozygous CETP deficiency, unusual for markedly elevated serum triglyceride alongside elevated HDL cholesterol (most CETP deficiency cases show normal or reduced triglyceride), was compared with two heterozygous CETP-deficient relatives and ten normal controls during an oral fat tolerance test. His serum triglyceride, HDL-C, apo-AI and apo-B48 were significantly higher and LDL cholesterol lower than controls, with near-normal lipoprotein and hepatic lipase but markedly elevated angiopoietin-like-protein-3. After the fat load, his remnant-like particle triglyceride and total triglyceride rose significantly, but remnant-like particle cholesterol did not increase, indicating that remnant triglyceride and cholesterol formation are controlled independently in CETP deficiency and that CETP deficiency itself may not be atherogenic unless remnant particles are also elevated.
Original abstract
Background: We found a unique cholesteryl ester transfer protein (CETP) deficient case with markedly elevated serum triglyceride (TG) as well as high-density lipoprotein cholesterol (HDL-C) levels. Most of the CETP deficiency cases were reported to have normal or reduced serum TG with elevated HDL-C.
Methods: The case subject was a 40-year-old male with a compound heterozygous CETP deficiency. Two heterozygous CETP deficient cases and 10 normal volunteers were also recruited as controls. They underwent an oral fat tolerance test (OFTT) and their blood was taken at fasting and during the OFTT to be used for laboratory tests.
Results: The case subject had apolipoprotein E (apo-E) phenotype 4/2 with fatty liver but without any cardiovascular disease. His serum TG, HDL-C, apo-AI and apo-B48 levels were significantly higher, but the low-density lipoprotein cholesterol level was lower than controls. Although post-heparin plasma lipoprotein lipase and hepatic lipase (both mass and activity) were nearly normal, the serum level of angiopoietin-like-protein-3 was extremely elevated. While his serum remnant-like particles-TG (RLP-TG) and total TG levels significantly increased after a fat load, the RLP-cholesterol (RLP-C) level did not increase during OFTT.
Conclusions: The case subject was different from the common CETP deficient cases reported previously. Also, the results indicated that the metabolic pathways of RLP-C and RLP-TG formation in the postprandial state are controlled independently in CETP deficient cases. CETP deficiency itself may not be atherogenic, while one with elevated RLPs may be atherogenic. These cases may have raised the controversy of whether CETP deficiency is atherogenic or not.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.