Cholesterylester transfer protein

Cholesteryl ester transfer protein, plasma
PDB rendering based on 2obd.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2OBD, 4EWS, 4F2A
Identifiers
Symbols	CETP ; BPIFF; HDLCQ10
External IDs	OMIM: 118470 HomoloGene: 47904 ChEMBL: 3572 GeneCards: CETP Gene
Gene ontology Molecular function • lipid transporter activity • phospholipid transporter activity • lipid binding • cholesterol binding • cholesterol transporter activity • triglyceride binding • phosphatidylcholine binding Cellular component • extracellular region • extracellular space • vesicle • high-density lipoprotein particle • extracellular exosome Biological process • triglyceride metabolic process • lipid transport • receptor-mediated endocytosis • cholesterol metabolic process • negative regulation of macrophage derived foam cell differentiation • regulation of cholesterol efflux • phospholipid transport • cholesterol transport • triglyceride transport • very-low-density lipoprotein particle remodeling • low-density lipoprotein particle remodeling • high-density lipoprotein particle remodeling • lipoprotein metabolic process • cholesterol homeostasis • reverse cholesterol transport • small molecule metabolic process • phosphatidylcholine metabolic process • lipid homeostasis • phospholipid homeostasis • triglyceride homeostasis Sources: Amigo / QuickGO
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: 56.96 – 56.98 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 heteroexchange, trading a triglyceride for a cholesteryl ester or a cholesteryl ester for a triglyceride.

Genetics

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

Role in disease

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

Elaidic acid, a major component of trans fat, increases CETP activity.

Pharmacology

See also: CETP inhibitor

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. 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. 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, and, in a trial of a combination of torcetrapib and atorvastatin, an increase in cardiovascular events and mortality.

A compound related to torcetrapib, Dalcetrapib (investigative name JTT-705/R1658), was also studied, but trials have ceased. It increases HDL levels by 30%, as compared to 60% by torcetrapib. Two CETP inhibitors are currently under development. One is Merck's MK-0859 anacetrapib, which in initial studies did not increase blood pressure. The other is Eli Lilly's evacetrapib, which failed in Phase 3 trials.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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|px|alt=Statin Pathway edit]]

File:StatinPathway_WP430.png

Statin Pathway edit

External links

• Cholesterol ester transfer proteins at the US National Library of Medicine Medical Subject Headings (MeSH)