Genetics
CETP TaqIB genotype cuts cardiovascular risk 30% in non-smokers but not smokers in WOSCOPS (Eur Heart J 2003)
Original title: A polymorphism of the cholesteryl ester transfer protein gene predicts cardiovascular events in non-smokers in the West of Scotland Coronary Prevention Study
In the West of Scotland Coronary Prevention Study, 498 cardiovascular cases and 1108 controls were genotyped for CETP TaqIB, C(-631)A, C(-629)A, I405V, and D442G polymorphisms. TaqIB2 homozygotes (B2B2) had a 30% lower risk of a cardiovascular event than B1B1 homozygotes (OR 0.70, 95% CI 0.51-0.96, P=0.03), a relationship only marginally attenuated by adjusting for HDL or LDL diameter. This dose-dependent TaqIB-risk association was seen only in non-smokers, not smokers, though pravastatin's treatment benefit did not differ significantly across TaqIB genotypes (OR 0.71, 0.68, 0.61 for B1B1, B1B2, B2B2). None of the other CETP polymorphisms tested showed significant cardiovascular risk associations, and haplotype analysis added no further information beyond the individual TaqIB result.
Original 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, CI(95)0.51-0.96, 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.