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European Heart Journal 2003 24(20):1833-1842; doi:10.1016/j.ehj.2003.07.001
Copyright © 2003 by the European Society of Cardiology.
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Clinical research

A polymorphism of the cholesteryl ester transfer protein gene predicts cardiovascular events in non-smokers in the West of Scotland Coronary Prevention Study

Dilys J Freemana,{dagger},*, Nilesh J Samanib, Valerie Wilsona, Alex D McMahonc, Peter S Braundb, Suzanne Chengd, Muriel J Caslakee, Chris J Packarde and Dairena Gaffneye on behalf of the West of Scotland Study Group

a Department of Biological Sciences, University of Durham, Durham, UK
{dagger} Present address: Department of Obstetrics and Gynaecology, University of Glasgow, Royal Infirmary, Glasgow, UK
b Division of Cardiology, University of Leicester, Glenfield Hospital, Leicester, UK
c Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
d Department of Human Genetics, Roche Molecular Systems, Inc, Alameda, California, USA
e Department of Pathological Biochemistry, Glasgow Royal Infirmary University NHS Trust, Glasgow, UK

* Correspondence to: Dr D. J. Freeman, University of Glasgow, Obstetrics and Gynaecology, 3rd Floor Queen Elizabeth Building Royal Infirmary, Glasgow G31 2ER, UK. Tel: +44 141 211 4706; Fax: +44 141 552 0873
E-mail address: d.freeman{at}clinmed.gla.ac.uk

Received 14 April 2003; revised 22 July 2003; accepted 31 July 2003

Abstract

Aim The association of cholesteryl ester transfer protein (CETP) gene polymorphisms with risk of a cardiovascular event and whether any association was explained by an influence on high-density lipoprotein (HDL) levels or low-density lipoprotein (LDL) size was tested in the West of Scotland Coronary Prevention Study (WOSCOPS). Gene-smoking and gene-treatment interactions were investigated.

Methods and results Cases (n=498) and controls (n=1108) were typed for TaqIB, C(–631)A, C(–629)A, I405V and D442G CETP polymorphisms. Homozygotes for the TaqIB2 allele (B2B2) had a 30% reduced risk of a cardiovascular event (odds ratio [OR] 0.70, CI950.51–0.96, P=0.03) compared to B1B1 homozygotes. Inclusion of HDL or LDL diameter in multivariate analysis only marginally attenuated the relationships. Non-smokers, but not smokers, showed a dose-dependent association of risk with TaqIB genotype. Treatment benefit was not significantly different in B1B1 (OR 0.71, pravastatin vs placebo), B1B2 (OR 0.68) and B2B2 (OR 0.61) individuals. The other CETP polymorphisms studied had no significant association with cardiovascular risk. Haplotype analysis did not add to the information given by the individual polymorphisms.

Conclusion The association between CETP TaqIB genotype and cardiovascular risk is primarily in non-smokers, is not fully explained by effects on HDL levels or LDL size, and the benefit of pravastatin treatment was not influenced by this polymorphism.

Key Words: Atherosclerosis • Enzymes • Genetics • Lipoproteins • CETP • WOSCOPS


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