Genetics
First evidence that CETP Taq1B genotype can guide statin therapy: B2 carriers benefit strongly, B1B1 homozygotes do not (Am Heart J 2003)
Original title: The cholesteryl ester transfer protein Taq1B gene polymorphism predicts clinical benefit of statin therapy in patients with significant coronary artery disease
This study examined CETP Taq1B genotype, plasma HDL, and clinical events in 2531 consenting patients with significant coronary artery disease undergoing coronary arteriography, stratified by statin prescription at discharge and prospectively followed for all-cause mortality and myocardial infarction. Genotype frequencies were 32.9% B1B1, 50.3% B1B2, and 16.8% B2B2, with HDL reduced in B1B1 patients (33 vs 36 mg/dL for both other genotypes, P for trend=.003). Overall event rates did not differ by genotype, and statins showed no benefit in B1 homozygotes (24.8% untreated vs 24.2% treated), but significantly reduced events in B1B2 (28.0% vs 21.0%, P=.009) and B2B2 subjects (26.4% vs 17.4%, P=.048). After adjustment, B2 carriers had reduced events with statins (RR 0.62, 95% CI 0.45-0.86) while B1B1 patients did not (RR 1.09, 95% CI 0.70-1.7; P for interaction=.02), with similarly stronger benefit for B1B2 and B2B2 in the death-alone endpoint.
Original abstract
Background: Cholesteryl ester transfer protein (CETP) regulates plasma lipid distribution. A polymorphism in the CETP gene (Taq1B) is associated with CETP activity, HDL concentration, atherosclerosis progression, and response to statins, and may influence cardiovascular (CV) events. We studied CETP Taq1B genotype, plasma HDL, and clinical events among all patients and patients stratified by statin treatment.
Methods: Consenting patients (n = 2531) with significant coronary artery disease (> or =1 lesion of > or =70% stenosis) undergoing coronary arteriography were genotyped, grouped by statin prescription at hospital discharge, and prospectively followed-up for the outcomes of all-cause mortality and myocardial infarction.
Results: CETP Taq1B genotype frequencies were: B1B1, 32.9%; B1B2, 50.3%; and B2B2 16.8%. Plasma HDL was reduced for B1B1 patients (33 +/- 12 mg/dL, vs 36 +/- 13 mg/dL and 36 +/- 13 mg/dL for B1B2 and B2B2, respectively, P for trend =.003). Overall, event rates did not differ between genotypes. Event rates were similar among untreated (24.8%) and statin-treated (24.2%) B1 homozygotes (P = NS); statins significantly reduced events for B1B2 subjects (28.0% vs 21.0%, P =.009) and for B2B2 subjects (26.4% vs 17.4%, P =.048). Therapeutic benefit for B2 carriers remained after adjustment for covariates, and regression interaction analysis showed that B2 carriers experienced reduced events (relative risk [RR] 0.62, 95% CI 0.45-0.86), but statins did not benefit those with B1B1 (RR 1.09, 95% CI 0.70-1.7; P for interaction =.02). Findings were similar for the end point of death alone, although a modest benefit was seen in B1B1 patients (RR 0.67, P =.10), in addition to the strong benefit for B1B2 (RR 0.53, P =.001) and B2B2 (RR 0.28, P =.001).
Conclusions: The CETP Taq1B polymorphism is associated with differential HDL levels but no significant differential in CV risk in the absence of treatment. Importantly, however, CV event reduction by statin therapy is substantially enhanced in the presence of a B2 allele. Our findings suggest, for the first time, the potential of CETP Taq1B genotyping to enable more effective, pharmacogenetically directed therapy.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.