A Novel Mutation in the Human Plasma Cholesteryl Ester Transfer Protein (CETP) Gene Leading to CETP-Deficiency in a Nova Scotian Patient: A Review of CETP Deficiency

Peter J. Dolphin


Human Cholesteryl Ester Transfer Protein (CETP) is a 476-residue hydrophobic plasma glycoprotein which catalyzes the hetero-exchange and net mass transfer of cholesteryl esters and triacylglycerols between plasma High Density Lipoprotein (HDL) and Very Low Density (VLDL) and Low Density Lipoproteins (LDL). CETP, together with the plasma enzyme Lecithin:Cholesterol Acyltransferase (LCAT), form integral parts of the Reverse Cholesterol Transport pathway by which cholesterol is removed from peripheral tissues and transported back to the liver for excretion or reutilization. We have recently identified a novel mutation (CT) at nucleotide 836 in Exon 9 of the Cholesteryl Ester Transfer Protein gene from a Caucasian subject resident in Nova Scotia. The patient is homozygous for the mutation which results in the conversion of 268 Arg into a STOP codon and a truncated, dysfunctional protein. This patient is the first Caucasian North American subject reported to have CETP deficiency. The majority of other subjects are of Japanese ancestry. Biochemically, homozygous CETP deficiency is characterized by a moderate hypercholesterolemia (7±0.8 mmol/L) entirely attributable to an elevated HDL cholesterol (4.2±1.0 mmol/L). LDL cholesterol is usually low (2±0.8 mmol/L). Lipoprotein composition is markedly altered with the HDL much larger, cholesteryl ester enriched and triglyceride poor: the LDL is polydisperse. triglyceride enriched, with a lower proportion of cholesteryl ester per particle. The VLDL is similarly cholesteryl ester poor. Here we review the structure and function of CETP. the consequences of CETP deficiency and hence its diagnosis and discuss the current opinions concerning the atherosclerotic risk associated with CETP deficiency and thus the advisability of treating this disorder with cholesterol lowering drugs.

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DOI: https://doi.org/10.15273/dmj.Vol26No2.4411


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