View source for Cholesterylester transfer protein

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{{GNF_Protein_box
 | image = PBB_Protein_CETP_image.jpg
 | image_source = [[Protein_Data_Bank|PDB]] rendering based on 2obd.
 | Name = Cholesteryl ester transfer protein, plasma
 | HGNCid = 1869
 | Symbol = CETP
 | AltSymbols =; 
 | OMIM = 118470
 | ECnumber =  
 | Homologene = 47904
 | MGIid =  
 | GeneAtlas_image1 = PBB_GE_CETP_206210_s_at_tn.png
 | Function = {{GNF_GO|id=GO:0003824 |text = catalytic activity}} {{GNF_GO|id=GO:0008289 |text = lipid binding}} 
 | Component = 
 | Process = {{GNF_GO|id=GO:0006629 |text = lipid metabolic process}} {{GNF_GO|id=GO:0006869 |text = lipid transport}} {{GNF_GO|id=GO:0008202 |text = steroid metabolic process}} {{GNF_GO|id=GO:0008203 |text = cholesterol metabolic process}} 
 | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1071
    | Hs_Ensembl = ENSG00000087237
    | Hs_RefseqProtein = NP_000069
    | Hs_RefseqmRNA = NM_000078
    | Hs_GenLoc_db =  
    | Hs_GenLoc_chr = 16
    | Hs_GenLoc_start = 55553263
    | Hs_GenLoc_end = 55575257
    | Hs_Uniprot = P11597
    | Mm_EntrezGene =  
    | Mm_Ensembl =  
    | Mm_RefseqmRNA =  
    | Mm_RefseqProtein =  
    | Mm_GenLoc_db =  
    | Mm_GenLoc_chr =  
    | Mm_GenLoc_start =  
    | Mm_GenLoc_end =  
    | Mm_Uniprot =  
  }}
}}
{{SI}}
{{CMG}}



'''Cholesteryl ester transfer protein''' (CETP) (also called '''plasma lipid transfer protein''') is a [[blood plasma|plasma]] [[protein]] that facilitates the transport of [[cholesteryl ester]]s and [[triglyceride]]s between the [[lipoprotein]]s. It collects triglycerides from [[Very low density lipoprotein|very low density]] or [[low density lipoprotein]]s (VLDL or LDL) and exchanges them for cholesteryl esters from [[high density lipoprotein]]s (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]].<ref name=Zhong1996>{{cite journal |author= Zhong S, Sharp DS, Grove JS, Bruce C, Yano K, Curb JD, Tall AR |year=1996 |month=Jun |title= Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels |journal=J Clin Invest |volume=97 |issue=12 |pages=2917-23 |id=PMID 8675707 |url=http://www.jci.org/cgi/content/full/97/12/2917}}</ref> In contrast, a polymorphism (I405V) of the ''CETP'' gene leading to lower serum levels has also been linked to exceptional longevity.<ref>{{cite journal |author=Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR |year= 2003|month=Oct |title=Unique lipoprotein phenotype and genotype associated with exceptional longevity |journal=JAMA |volume=290 |issue=15 |pages=2030-40 |id=PMID 14559957 |url=http://jama.ama-assn.org/cgi/content/full/290/15/2030}}</ref> However, this mutation also increases the prevalence of coronary heart disease in patients with hypertriglyceridemia.<ref>{{cite journal |author=Bruce C, Sharp DS, Tall AR |year=1998|month=May |title= |journal=J Lipid Res |volume=39 |issue=5 |pages=1071-8  |id=PMID 9610775 |url=http://www.jlr.org/cgi/content/full/39/5/1071}}</ref> The D442G mutation, which lowers CETP levels and increases HDL levels also increases coronary heart disease.<ref name=Zhong1996/>

[[Elaidic acid]]&mdash;a major component of [[trans fat]]&mdash;increases CETP activity.<ref name="pmid8018112">{{cite journal |author=Abbey M, Nestel PJ |title=Plasma cholesteryl ester transfer protein activity is increased when trans-elaidic acid is substituted for cis-oleic acid in the diet |journal=Atherosclerosis |volume=106 |issue=1 |pages=99–107 |year=1994 |pmid=8018112|doi=10.1016/0021-9150(94)90086-8}}</ref>

==Pharmacology==
As [[High density lipoprotein|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.<ref>{{cite journal |author=Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR |year=2003 |month=Feb |title=Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis |journal=Arterioscler Thromb Vasc Biol |volume=23 |issue=2 |pages=160-7 |id=PMID 12588754 |url=http://atvb.ahajournals.org/cgi/content/full/23/2/160}}</ref> Specifically, 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) in a 2004 study.<ref>{{cite journal |author=Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ |year=2004 |month=Apr |title=Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol |journal=N Engl J Med |volume=350 |issue=15 |pages=1505-15 |id=PMID 15071125 |url=http://content.nejm.org/cgi/content/full/350/15/1505}}</ref> 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,<ref>{{cite journal |author=Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, Ruzyllo W, Bachinsky WB, Lasala GP, Tuzcu EM; ILLUSTRATE Investigators |year=2007 |month=Mar |title=Effect of torcetrapib on the progression of coronary atherosclerosis |journal=N Engl J Med |volume=356 |issue=13 |pages=1304-16 |id=PMID 17387129 |url=http://content.nejm.org/cgi/content/full/356/13/1304}}</ref><ref>{{cite journal |author=Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, Revkin JH, Grobbee DE, Riley WA, Shear CL, Duggan WT, Bots ML; RADIANCE 1 Investigators. |year=2007 |month=Apr |title=Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia |journal=N Engl J Med |volume=356 |issue=16 |pages=1620-30 |id=PMID 17387131 |url=http://content.nejm.org/cgi/content/abstract/356/16/1620}}</ref> and (in a trial of a combination of torcetrapib and atorvastatin) an increase in cardiovascular events and mortality.<ref name=FDA2006>{{cite press release |title=Pfizer Stops All Torcetrapib Clinical Trials in Interest of Patient Safety |publisher=U.S. Food and Drug Administration |date=3 December 2006 |url=http://www.fda.gov/bbs/topics/news/2006/new01514.html}}</ref>

A compound related to torcetrapib, going by the investigative name JTT-705/R1658, is undergoing studies.<ref>{{cite journal |author=El Harchaoui K, van der Steeg WA, Stroes ES, Kastelein JJ |year=2007 |month=Aug |title=The role of CETP inhibition in dyslipidemia |journal=Curr Atheroscler Rep |volume=9 |issue=2 |pages=125-33 |id=PMID 17877921}}</ref> It increases HDL levels by 30% (as compared to 60% by torcetrapib).<ref>{{cite journal |author=de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf J, Zwinderman AH, Posma JL, van Tol A, Kastelein JJ |year=2002 |month=May |title=Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study |journal=Circulation |volume=105 |issue=18 |pages=2159-65 |id=PMID 11994249  |url=http://circ.ahajournals.org/cgi/content/full/circulationaha;105/18/2159}}</ref>. Another CETP inhibitor under development is Merck's MK-0859 [[anacetrapib]], which in initial studies has been shown not to increase blood pressure.<ref>{{cite news |author=Reuters|title=Merck announces its investigational CETP-Inhibitor, MK-0859, produced positive effects on lipids with no observed blood pressure changes | url=http://www.reuters.com/article/inPlayBriefing/idUSIN20071004163052MRK20071004 |publisher=Reuters, Inc. |date=4 October 2007 |accessdate=2007-11-04}}</ref>

==References==
{{Reflist|2}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=Okajima F |title=[Distribution of sphingosine 1-phosphate in plasma lipoproteins and its role in the regulation of the vascular cell functions] |journal=Tanpakushitsu Kakusan Koso |volume=47 |issue= 4 Suppl |pages= 480-7 |year= 2002 |pmid= 11915346 |doi=  }}
*{{cite journal  | author=Barter PJ, Brewer HB, Chapman MJ, ''et al.'' |title=Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. |journal=Arterioscler. Thromb. Vasc. Biol. |volume=23 |issue= 2 |pages= 160-7 |year= 2003 |pmid= 12588754 |doi=  }}
*{{cite journal  | author=Dallinga-Thie GM, Dullaart RP, van Tol A |title=Concerted actions of cholesteryl ester transfer protein and phospholipid transfer protein in type 2 diabetes: effects of apolipoproteins. |journal=Curr. Opin. Lipidol. |volume=18 |issue= 3 |pages= 251-7 |year= 2007 |pmid= 17495597 |doi= 10.1097/MOL.0b013e3280e12685 }}
}}
{{refend}}

==External links==
* {{MeshName|Cholesterol+ester+transfer+proteins}}

{{Glycoproteins}}
{{Carrier proteins}}

[[Category:Blood proteins]]
[[Category:Cardiology]]

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