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CLINICAL RESEARCH: GENETICS AND CARDIOVASCULAR DISEASE

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

Greetje J. de Grooth, MD, PhD^*, Kim E. Zerba, PhD, Shu-Pang Huang, PhD, Zenta Tsuchihashi, PhD, Todd Kirchgessner, PhD, René Belder, MD, Priya Vishnupad, BSc, Beihong Hu, MSc, Anke H. E. M. Klerkx, PhD^*, Aeilko H. Zwinderman, PhD, J. Wouter Jukema, MD, PhD, Frank M. Sacks, MD, PhD^||, John J. P. Kastelein, MD, PhD^*,* and Jan Albert Kuivenhoven, PhD^*

^* Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Bristol-Myers Squibb Co, Princeton, New Jersey, USA
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
^|| Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA

Manuscript received March 26, 2003; revised manuscript received July 9, 2003, accepted August 5, 2003.

^* Reprint requests and correspondence: Prof. Dr. John J.P. Kastelein, Department of Vascular Medicine G1-146, Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands.
e.vanDongen{at}amc.uva.nl

OBJECTIVES: 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.

Abbreviations and Acronyms   CARE = Cholesterol And Recurrent Events study   CETP = cholesteryl ester transfer protein   CHD = coronary heart disease   HDL-c = high-density lipoprotein cholesterol   LDL-c = low-density lipoprotein cholesterol   MI = myocardial infarction

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