Common genetic variation of the cholesteryl ester transfer protein gene strongly predicts future cardiovascular death in patients with coronary artery disease

AbstractObjectivesWe sought to evaluate the association between cholesteryl ester transfer protein (CETP) genotypes and the risk of future cardiovascular mortality in patients with coronary artery disease (CAD).BackgroundPolymorphisms of the CETPgene influence CETP activity and high-density lipoprotein (HDL) cholesterol concentration and might affect the long-term prognosis and response to statin therapy in patients with CAD.MethodsWe used serum samples and deoxyribonucleic acid collected at baseline from a prospective cohort of 1,211 patients with CAD prospectively followed up (median follow-up of 4.1 years), 82 of whom experienced a fatal cardiovascular event. The CETP/C-629Aand I405Vpolymorphisms, CETP activity, and HDL cholesterol were determined.ResultsPatients carrying the −629Aallele had significantly lower CETPactivity and higher HDL cholesterol levels. There was a significant association between this polymorphism and the risk of future cardiovascular death. Mortality decreased from 10.8% in CChomozygotes to 4.6% in CAheterozygotes and 4.0% in AAhomozygotes (p < 0.0001). This association was independent of potential confounders, particularly HDL cholesterol and CETP activity levels. The clinical benefit of statin therapy was restricted to CChomozygotes, in whom cardiovascular mortality was divided by half (p = 0.01 for treatment × genotype interaction). Similar trends were observed with the CETP/I405Vpolymorphism, but these effects seemed to be mainly the consequence of linkage disequilibrium with the CETP/C-629Apolymorphism.ConclusionsIn patients with CAD, the CETP/−629Aallele had a strong protective effect on future mortality from cardiovascular causes, independent of its role on HDL cholesterol and CETP activity levels. Additionally, this common polymorphism appeared to predict which patients with CAD will experience a survival benefit from statin therapy