Cholesteryl ester transfer protein: Difference between revisions
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'''Cholestrol ester transfer protein''' (CETP) is a [[blood plasma|plasma]] [[protein]] that converts [[high density lipoprotein]] (HDL) into [[intermediate density lipoprotein]] (IDL). Its exact mechanism of action is still uncertain. Apart from converting HDL to IDL, it also appears to mediate uptake of HDL by the [[liver]]. |
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==Genetics== |
==Genetics== |
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Revision as of 03:04, 6 November 2006
Cholestrol ester transfer protein (CETP) is a plasma protein that converts high density lipoprotein (HDL) into intermediate density lipoprotein (IDL). Its exact mechanism of action is still uncertain. Apart from converting HDL to IDL, it also appears to mediate uptake of HDL by the liver.
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. In contrast, a polymorphism of the CETP gene leading to lower serum levels has also been linked to exceptional longevity (Barzilai et al 2003).
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 (Barter et al 2003). 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 (Brousseau et al). In a recent study, patients taking torcetrapib combined with atorvastatin (Lipitor), experienced an increase systolic blood pressure. (Thuren T et al.)
References
- 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.
- 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.
- 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.
External links
- Online Mendelian Inheritance in Man (OMIM): 118470 (CETP) and Online Mendelian Inheritance in Man (OMIM): 607322 (CETP deficiency)