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Cholesteryl ester transfer protein, plasma
PDB rendering based on 2obd.
Available structures
2obd
Identifiers
Symbols	CETP;
External IDs	OMIM: 118470 HomoloGene: 47904 GeneCards: CETP Gene
Gene ontology Molecular function • catalytic activity • lipid binding Biological process • lipid metabolic process • lipid transport • steroid metabolic process • cholesterol metabolic process
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1071	n/a
Ensembl	ENSG00000087237	n/a
UniProt	P11597	n/a
RefSeq (mRNA)	NM_000078	n/a
RefSeq (protein)	NP_000069	n/a
Location (UCSC)	Chr 16: 55.55 - 55.58 Mb	n/a
PubMed search	[1]	n/a

Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low-density (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a homoexchange, trading a triglyceride for a triglyceride or a cholesteryl ester for a cholesteryl ester.

Genetics

The CETP gene is located on the sixteenth chromosome (16q21).

Role in disease

Rare mutations leading to increased function of CETP have been linked to accelerated atherosclerosis.^[1] In contrast, a polymorphism (I405V) of the CETP gene leading to lower serum levels has also been linked to exceptional longevity.^[2] However, this mutation also increases the prevalence of coronary heart disease in patients with hypertriglyceridemia.^[3] The D442G mutation, which lowers CETP levels and increases HDL levels also increases coronary heart disease.^[1]

Elaidic acid, a major component of trans fat, increases CETP activity.^[4]

Pharmacology

As HDL can alleviate atherosclerosis and other cardiovascular diseases, and certain disease states such as the metabolic syndrome feature low HDL, pharmacological inhibition of CETP is being studied as a method of improving HDL levels.^[5] To be specific, in a 2004 study, the small molecular agent torcetrapib was shown to increase HDL levels, alone and with a statin, and lower LDL when co-administered with a statin.^[6] Studies into cardiovascular endpoints, however, were largely disappointing. While they confirmed the change in lipid levels, most reported an increase in blood pressure, no change in atherosclerosis,^[7][8] and, in a trial of a combination of torcetrapib and atorvastatin, an increase in cardiovascular events and mortality.^[9]

A compound related to torcetrapib, with the investigative name JTT-705/R1658, is also being studied.^[10] It increases HDL levels by 30%, as compared to 60% by torcetrapib.^[11] Another CETP inhibitor under development is Merck's MK-0859 anacetrapib, which in initial studies is not shown to increase blood pressure.^[12]

References

Further reading

PDB Gallery 2obd: Crystal Structure of Cholesteryl Ester Transfer Protein

External links

• MeSH Cholesterol+ester+transfer+proteins