Cholesterylester transfer protein

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cholesteryl ester transfer protein, plasma
Identifiers
Symbol	CETP
HUGO	1869
Entrez	1071
OMIM	118470
RefSeq	NM_000078
UniProt	P11597
Other data
Locus	Chr. 16 q13

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 picks up triglycerides from Very Low- or Low- Density Lipoproteins (VLDL or LDL) and can exchange them for cholesteryl esters from High Density Lipoproteins (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.

1 Genetics
2 Role in disease
3 Pharmacology
4 References
5 External links

[edit] Genetics

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

[edit] Role in disease

Rare mutations leading to increased function of CETP have been linked to accelerated atherosclerosis. In contrast, a polymorphism of the CETP gene leading to lower serum levels has also been linked to exceptional longevity.^[1]

[edit] Pharmacology

As HDL has a protective function in atherosclerosis and cardiovascular disease, and certain disease states (such as the metabolic syndrome) feature low HDL, pharmacological inhibition of CETP is being studied as a method to improve HDL levels.^[2] Specifically, the small molecular agent torcetrapib has been shown to increase HDL levels (alone and with a statin) and lower LDL (when co-administered with a statin) in a 2004 study.^[3]

Patients taking torcetrapib combined with atorvastatin (Lipitor), experienced an increase systolic blood pressure.^[4] All development of torcetrapib was halted on December 2nd 2006 by its maker, Pfizer, because the drug increased deaths and cardiovascular events. In the days following, Pfizer stock lost 11% of its value, the largest such drop in a 10 year period.

This unexpected result calls into question the very role of cholesterol in heart disease since the drug both lowered the presumed "bad" [LDL] cholesterol substantially while increasing the presumed "good" [HDL] more than any other drug ever tested, including niacin. It should be noted that HDL-raising niacin [nicotinic acid, vitamin B3], acting through different pathways, did have beneficial effects in heart disease in the Coronary Drug Project study, when compared with placebo.

[edit] References

^ Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 2003;290:2030-40. PMID 14559957.
^ Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol 2003;23:160-7. PMID 12588754.
^ Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med 2004;350:1505-15. PMID 15071125.
^ Thuren T, Longcore A, Powell C, et al. Effects of torcetrapib and/or atorvastatin on HDL and LDL particle size and composition: results from a phase 2 trial. American College of Cardiology 2006 Scientific Sessions; March 11-14, 2006; Atlanta, GA. Poster 981-195.