The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study: no interaction with the response to pravastatin therapy and no effects on cardiovascular outcome: a prospective analysis of the CETP TaqIB polymorphism on cardiovascular outcome and interaction with cholesterol-lowering therapy.
OBJECTIVE
On the basis of quantitative coronary angiography data, the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism has been postulated to predict the progression of coronary atherosclerosis and response to cholesterol-lowering therapy.


BACKGROUND
Cholesteryl ester transfer protein mediates the exchange of lipids between anti-atherogenic high-density lipoprotein (HDL) and atherogenic apolipoprotein B containing lipoproteins and therefore plays a key role in human lipid metabolism. Hence, CETP gene polymorphisms may alter susceptibility to atherosclerosis.


METHODS
To investigate the significance of the CETP TaqIB gene polymorphism with respect to clinical end points, we used the Cholesterol And Recurrent Events (CARE) cohort. The CARE study was designed to investigate the effect of five years of pravastatin therapy on coronary events.


RESULTS
We found that the odds ratios for the primary end point were not significantly different from unity for the three genetic subgroups after five years of placebo treatment. Furthermore, pravastatin induced similar changes in total cholesterol, low-density lipoprotein cholesterol, and HDL cholesterol among TaqIB genotypes, and both nonfatal myocardial infarction and deaths from coronary heart disease were reduced to the same extent in all three genotypes.


CONCLUSIONS
In the CARE cohort, the CETP TaqIB polymorphism does not predict cardiovascular events or discriminate between those who will or will not benefit from pravastatin treatment.
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Greetje J
GJ
de Grooth
Kim E
KE
Zerba
Shu-Pang
SP
Huang
Zenta
Z
Tsuchihashi
Todd
T
Kirchgessner
René
R
Belder
Priya
P
Vishnupad
Beihong
B
Hu
Anke H E M
AH
Klerkx
Aeilko H
AH
Zwinderman
J Wouter
JW
Jukema
Frank M
FM
Sacks
John J P
JJ
Kastelein
Jan Albert
JA
Kuivenhoven
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; C059680:DNA modification methylase TaqI; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D017035:Pravastatin